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{{Infobox_gene}}
{{Infobox_gene}}
'''Tuberous sclerosis 1 (TSC1)''', also known as '''Hamartin''', is a [[protein]] that in humans is encoded by the ''TSC1'' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: TSC1 tuberous sclerosis 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7248| accessdate = }}</ref>
'''Tuberous sclerosis 1 (TSC1)''', also known as '''Hamartin''', is a [[protein]] that in humans is encoded by the ''TSC1'' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: TSC1 tuberous sclerosis 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7248| access-date = }}</ref>


== Function ==
== Function ==
TSC1 forms a multi-protein complex with [[TSC2]] and [[TBC1D7]] known as the TSC complex. This complex negatively regulates [[mTORC1]] signaling by functioning as a GTPase-activating protein (GAP) for the small GTPase [[Rheb]], an essential activator of mTORC1. The TSC complex has been implicated as a [[tumor suppressor]].
TSC1 functions as a co-chaperone which inhibits the ATPase activity of the chaperone [[Hsp90|Hsp90 (heat shock protein-90)]] and decelerates its chaperone cycle.  Tsc1 functions as a facilitator of Hsp90 in chaperoning the kinase and non-kinase clients including Tsc2, therefore preventing their ubiquitination and degradation in the proteasome.<ref name=":0">{{cite journal|vauthors=Woodford MR, Sager RA, Marris E, Dunn DM, Blanden AR, Murphy RL, Rensing N, Shapiro O, Panaretou B, Prodromou C, Loh SN, Gutmann DH, Bourboulia D, Bratslavsky G, Wong M, Mollapour M|date=December 2017|title=Tumor suppressor Tsc1 is a new Hsp90 co-chaperone that facilitates folding of kinase and non-kinase clients|journal=The EMBO Journal|volume=36|issue=24|pages=3650–3665|doi=10.15252/embj.201796700|pmc=5730846|pmid=29127155}}</ref> TSC1, [[TSC2]] and [https://www.ncbi.nlm.nih.gov/pubmed/22795129 TBC1D7] is a multi-protein complex also known as the TSC complex. This complex negatively regulates [[mTORC1]] signaling by functioning as a GTPase-activating protein (GAP) for the small GTPase [[Rheb]], an essential activator of mTORC1. The TSC complex has been implicated as a [[tumor suppressor]].


== Clinical significance ==
== Clinical significance ==
Defects in this gene can cause [[tuberous sclerosis]], due to a functional impairment of the TSC complex.{{Citation needed|date=June 2013}} Defects in TSC1 may also be a cause of focal [[cortical dysplasia]].{{Citation needed|date=June 2013}} TSC1 may be involved in protecting brain [[neurons]] in the CA3 region of the [[hippocampus]] from the effects of [[stroke]].<ref name="pmid23435171">{{cite journal | vauthors = Papadakis M, Hadley G, Xilouri M, Hoyte LC, Nagel S, McMenamin MM, Tsaknakis G, Watt SM, Drakesmith CW, Chen R, Wood MJ, Zhao Z, Kessler B, Vekrellis K, Buchan AM | title = Tsc1 (hamartin) confers neuroprotection against ischemia by inducing autophagy | journal = Nat. Med. | volume = 19 | issue = 3 | pages = 351–7 |date=March 2013 | pmid = 23435171 | doi = 10.1038/nm.3097 | pmc=3744134}}</ref>
Defects in this gene can cause [[tuberous sclerosis]], due to a functional impairment of the TSC complex.{{Citation needed|date=June 2013}} Defects in TSC1 may also be a cause of focal [[cortical dysplasia]].{{Citation needed|date=June 2013}} TSC1 may be involved in protecting brain [[neurons]] in the CA3 region of the [[hippocampus]] from the effects of [[stroke]].<ref name="pmid23435171">{{cite journal | vauthors = Papadakis M, Hadley G, Xilouri M, Hoyte LC, Nagel S, McMenamin MM, Tsaknakis G, Watt SM, Drakesmith CW, Chen R, Wood MJ, Zhao Z, Kessler B, Vekrellis K, Buchan AM | title = Tsc1 (hamartin) confers neuroprotection against ischemia by inducing autophagy | journal = Nature Medicine | volume = 19 | issue = 3 | pages = 351–7 | date = March 2013 | pmid = 23435171 | pmc = 3744134 | doi = 10.1038/nm.3097 }}</ref>


== Interactions ==
== Interactions ==


TSC1 has been shown to [[Protein-protein interaction|interact]] with:
TSC1 has been shown to [[Protein-protein interaction|interact]] with:
* [[AKT1]],<ref name = pmid15342917>{{cite journal | vauthors = Roux PP, Ballif BA, Anjum R, Gygi SP, Blenis J | title = Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 101 | issue = 37 | pages = 13489–94 | year = 2004 | pmid = 15342917 | pmc = 518784 | doi = 10.1073/pnas.0405659101}}</ref><ref name = pmid12167664/>  
* [[AKT1]],<ref name = pmid15342917>{{cite journal | vauthors = Roux PP, Ballif BA, Anjum R, Gygi SP, Blenis J | title = Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 37 | pages = 13489–94 | date = September 2004 | pmid = 15342917 | pmc = 518784 | doi = 10.1073/pnas.0405659101 }}</ref><ref name = pmid12167664/>  
* [[NEFL]],<ref name = pmid12226091>{{cite journal | vauthors = Haddad LA, Smith N, Bowser M, Niida Y, Murthy V, Gonzalez-Agosti C, Ramesh V | title = The TSC1 tumor suppressor hamartin interacts with neurofilament-L and possibly functions as a novel integrator of the neuronal cytoskeleton | journal = J. Biol. Chem. | volume = 277 | issue = 46 | pages = 44180–6 | year = 2002 | pmid = 12226091 | doi = 10.1074/jbc.M207211200}}</ref>
*[[Hsp70|HSP70]] <ref name=":0" />
* [[PLK1]],<ref name = pmid16339216>{{cite journal | vauthors = Astrinidis A, Senapedis W, Henske EP | title = Hamartin, the tuberous sclerosis complex 1 gene product, interacts with polo-like kinase 1 in a phosphorylation-dependent manner | journal = Hum. Mol. Genet. | volume = 15 | issue = 2 | pages = 287–97 | year = 2006 | pmid = 16339216 | doi = 10.1093/hmg/ddi444}}</ref>  and
*[[Hsp90|HSP90]] <ref name=":0" />
* [[TSC2]].<ref name = pmid12167664>{{cite journal | vauthors = Dan HC, Sun M, Yang L, Feldman RI, Sui XM, Ou CC, Nellist M, Yeung RS, Halley DJ, Nicosia SV, Pledger WJ, Cheng JQ | title = Phosphatidylinositol 3-kinase/Akt pathway regulates tuberous sclerosis tumor suppressor complex by phosphorylation of tuberin | journal = J. Biol. Chem. | volume = 277 | issue = 38 | pages = 35364–70 | year = 2002 | pmid = 12167664 | doi = 10.1074/jbc.M205838200}}</ref><ref name = pmid16339216/><ref name = pmid11741833>{{cite journal | vauthors = Hodges AK, Li S, Maynard J, Parry L, Braverman R, Cheadle JP, DeClue JE, Sampson JR | title = Pathological mutations in TSC1 and TSC2 disrupt the interaction between hamartin and tuberin | journal = Hum. Mol. Genet. | volume = 10 | issue = 25 | pages = 2899–905 | year = 2001 | pmid = 11741833 | doi = 10.1093/hmg/10.25.2899}}</ref><ref name = pmid11290735>{{cite journal | vauthors = Aicher LD, Campbell JS, Yeung RS | title = Tuberin phosphorylation regulates its interaction with hamartin. Two proteins involved in tuberous sclerosis | journal = J. Biol. Chem. | volume = 276 | issue = 24 | pages = 21017–21 | year = 2001 | pmid = 11290735 | doi = 10.1074/jbc.C100136200}}</ref><ref name = pmid9580671>{{cite journal | vauthors = van Slegtenhorst M, Nellist M, Nagelkerken B, Cheadle J, Snell R, van den Ouweland A, Reuser A, Sampson J, Halley D, van der Sluijs P | title = Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products | journal = Hum. Mol. Genet. | volume = 7 | issue = 6 | pages = 1053–7 | year = 1998 | pmid = 9580671 | doi = 10.1093/hmg/7.6.1053}}</ref><ref name = pmid12176984>{{cite journal | vauthors = Nellist M, Goedbloed MA, de Winter C, Verhaaf B, Jankie A, Reuser AJ, van den Ouweland AM, van der Sluijs P, Halley DJ | title = Identification and characterization of the interaction between tuberin and 14-3-3zeta | journal = J. Biol. Chem. | volume = 277 | issue = 42 | pages = 39417–24 | year = 2002 | pmid = 12176984 | doi = 10.1074/jbc.M204802200}}</ref><ref name = pmid15340059>{{cite journal | vauthors = Li Y, Inoki K, Guan KL | title = Biochemical and functional characterizations of small GTPase Rheb and TSC2 GAP activity | journal = Mol. Cell. Biol. | volume = 24 | issue = 18 | pages = 7965–75 | year = 2004 | pmid = 15340059 | pmc = 515062 | doi = 10.1128/MCB.24.18.7965-7975.2004}}</ref><ref name = pmid12511557>{{cite journal | vauthors = Mak BC, Takemaru K, Kenerson HL, Moon RT, Yeung RS | title = The tuberin-hamartin complex negatively regulates beta-catenin signaling activity | journal = J. Biol. Chem. | volume = 278 | issue = 8 | pages = 5947–51 | year = 2003 | pmid = 12511557 | doi = 10.1074/jbc.C200473200}}</ref><ref name = pmid15851026>{{cite journal | vauthors = Ma L, Chen Z, Erdjument-Bromage H, Tempst P, Pandolfi PP | title = Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis | journal = Cell | volume = 121 | issue = 2 | pages = 179–93 | year = 2005 | pmid = 15851026 | doi = 10.1016/j.cell.2005.02.031}}</ref><ref name = pmid16636147>{{cite journal | vauthors = Cai SL, Tee AR, Short JD, Bergeron JM, Kim J, Shen J, Guo R, Johnson CL, Kiguchi K, Walker CL | title = Activity of TSC2 is inhibited by AKT-mediated phosphorylation and membrane partitioning | journal = J. Cell Biol. | volume = 173 | issue = 2 | pages = 279–89 | year = 2006 | pmid = 16636147 | pmc = 2063818 | doi = 10.1083/jcb.200507119}}</ref><ref name = pmid17077083>{{cite journal | vauthors = Cao Y, Kamioka Y, Yokoi N, Kobayashi T, Hino O, Onodera M, Mochizuki N, Nakae J | title = Interaction of FoxO1 and TSC2 induces insulin resistance through activation of the mammalian target of rapamycin/p70 S6K pathway | journal = J. Biol. Chem. | volume = 281 | issue = 52 | pages = 40242–51 | year = 2006 | pmid = 17077083 | doi = 10.1074/jbc.M608116200}}</ref><ref name = pmid14651849>{{cite journal | vauthors = Inoki K, Zhu T, Guan KL | title = TSC2 mediates cellular energy response to control cell growth and survival | journal = Cell | volume = 115 | issue = 5 | pages = 577–90 | year = 2003 | pmid = 14651849 | doi = 10.1016/S0092-8674(03)00929-2}}</ref><ref name = pmid15963462>{{cite journal | vauthors = Nellist M, Burgers PC, van den Ouweland AM, Halley DJ, Luider TM | title = Phosphorylation and binding partner analysis of the TSC1-TSC2 complex | journal = Biochem. Biophys. Res. Commun. | volume = 333 | issue = 3 | pages = 818–26 | year = 2005 | pmid = 15963462 | doi = 10.1016/j.bbrc.2005.05.175}}</ref><ref name = pmid16424383>{{cite journal | vauthors = Goncharova EA, Goncharov DA, Spaits M, Noonan DJ, Talovskaya E, Eszterhas A, Krymskaya VP | title = Abnormal growth of smooth muscle-like cells in lymphangioleiomyomatosis: Role for tumor suppressor TSC2 | journal = Am. J. Respir. Cell Mol. Biol. | volume = 34 | issue = 5 | pages = 561–72 | year = 2006 | pmid = 16424383 | pmc = 2644221 | doi = 10.1165/rcmb.2005-0300OC}}</ref><ref name = pmid14551205>{{cite journal | vauthors = Astrinidis A, Senapedis W, Coleman TR, Henske EP | title = Cell cycle-regulated phosphorylation of hamartin, the product of the tuberous sclerosis complex 1 gene, by cyclin-dependent kinase 1/cyclin B | journal = J. Biol. Chem. | volume = 278 | issue = 51 | pages = 51372–9 | year = 2003 | pmid = 14551205 | doi = 10.1074/jbc.M303956200}}</ref><ref name = pmid11741832>{{cite journal | vauthors = Nellist M, Verhaaf B, Goedbloed MA, Reuser AJ, van den Ouweland AM, Halley DJ | title = TSC2 missense mutations inhibit tuberin phosphorylation and prevent formation of the tuberin-hamartin complex | journal = Hum. Mol. Genet. | volume = 10 | issue = 25 | pages = 2889–98 | year = 2001 | pmid = 11741832 | doi = 10.1093/hmg/10.25.2889}}</ref><ref name = pmid11175345>{{cite journal | vauthors = Benvenuto G, Li S, Brown SJ, Braverman R, Vass WC, Cheadle JP, Halley DJ, Sampson JR, Wienecke R, DeClue JE | title = The tuberous sclerosis-1 (TSC1) gene product hamartin suppresses cell growth and augments the expression of the TSC2 product tuberin by inhibiting its ubiquitination | journal = Oncogene | volume = 19 | issue = 54 | pages = 6306–16 | year = 2000 | pmid = 11175345 | doi = 10.1038/sj.onc.1204009}}</ref><ref name = pmid10807585>{{cite journal | vauthors = Murthy V, Haddad LA, Smith N, Pinney D, Tyszkowski R, Brown D, Ramesh V | title = Similarities and differences in the subcellular localization of hamartin and tuberin in the kidney | journal = Am. J. Physiol. Renal Physiol. | volume = 278 | issue = 5 | pages = F737-46 | year = 2000 | pmid = 10807585 | doi = }}</ref><ref name = pmid10915759>{{cite journal | vauthors = Miloloza A, Rosner M, Nellist M, Halley D, Bernaschek G, Hengstschläger M | title = The TSC1 gene product, hamartin, negatively regulates cell proliferation | journal = Hum. Mol. Genet. | volume = 9 | issue = 12 | pages = 1721–7 | year = 2000 | pmid = 10915759 | doi = 10.1093/hmg/9.12.1721}}</ref>
* [[NEFL]],<ref name = pmid12226091>{{cite journal | vauthors = Haddad LA, Smith N, Bowser M, Niida Y, Murthy V, Gonzalez-Agosti C, Ramesh V | title = The TSC1 tumor suppressor hamartin interacts with neurofilament-L and possibly functions as a novel integrator of the neuronal cytoskeleton | journal = The Journal of Biological Chemistry | volume = 277 | issue = 46 | pages = 44180–6 | date = November 2002 | pmid = 12226091 | doi = 10.1074/jbc.M207211200 }}</ref>
* [[PLK1]],<ref name = pmid16339216>{{cite journal | vauthors = Astrinidis A, Senapedis W, Henske EP | title = Hamartin, the tuberous sclerosis complex 1 gene product, interacts with polo-like kinase 1 in a phosphorylation-dependent manner | journal = Human Molecular Genetics | volume = 15 | issue = 2 | pages = 287–97 | date = January 2006 | pmid = 16339216 | doi = 10.1093/hmg/ddi444 }}</ref>  and
* [[TSC2]].<ref name = pmid12167664>{{cite journal | vauthors = Dan HC, Sun M, Yang L, Feldman RI, Sui XM, Ou CC, Nellist M, Yeung RS, Halley DJ, Nicosia SV, Pledger WJ, Cheng JQ | title = Phosphatidylinositol 3-kinase/Akt pathway regulates tuberous sclerosis tumor suppressor complex by phosphorylation of tuberin | journal = The Journal of Biological Chemistry | volume = 277 | issue = 38 | pages = 35364–70 | date = September 2002 | pmid = 12167664 | doi = 10.1074/jbc.M205838200 }}</ref><ref name = pmid16339216/><ref name = pmid11741833>{{cite journal | vauthors = Hodges AK, Li S, Maynard J, Parry L, Braverman R, Cheadle JP, DeClue JE, Sampson JR | title = Pathological mutations in TSC1 and TSC2 disrupt the interaction between hamartin and tuberin | journal = Human Molecular Genetics | volume = 10 | issue = 25 | pages = 2899–905 | date = December 2001 | pmid = 11741833 | doi = 10.1093/hmg/10.25.2899 }}</ref><ref name = pmid11290735>{{cite journal | vauthors = Aicher LD, Campbell JS, Yeung RS | title = Tuberin phosphorylation regulates its interaction with hamartin. Two proteins involved in tuberous sclerosis | journal = The Journal of Biological Chemistry | volume = 276 | issue = 24 | pages = 21017–21 | date = June 2001 | pmid = 11290735 | doi = 10.1074/jbc.C100136200 }}</ref><ref name = pmid9580671>{{cite journal | vauthors = van Slegtenhorst M, Nellist M, Nagelkerken B, Cheadle J, Snell R, van den Ouweland A, Reuser A, Sampson J, Halley D, van der Sluijs P | title = Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products | journal = Human Molecular Genetics | volume = 7 | issue = 6 | pages = 1053–7 | date = June 1998 | pmid = 9580671 | doi = 10.1093/hmg/7.6.1053 }}</ref><ref name = pmid12176984>{{cite journal | vauthors = Nellist M, Goedbloed MA, de Winter C, Verhaaf B, Jankie A, Reuser AJ, van den Ouweland AM, van der Sluijs P, Halley DJ | title = Identification and characterization of the interaction between tuberin and 14-3-3zeta | journal = The Journal of Biological Chemistry | volume = 277 | issue = 42 | pages = 39417–24 | date = October 2002 | pmid = 12176984 | doi = 10.1074/jbc.M204802200 }}</ref><ref name = pmid15340059>{{cite journal | vauthors = Li Y, Inoki K, Guan KL | title = Biochemical and functional characterizations of small GTPase Rheb and TSC2 GAP activity | journal = Molecular and Cellular Biology | volume = 24 | issue = 18 | pages = 7965–75 | date = September 2004 | pmid = 15340059 | pmc = 515062 | doi = 10.1128/MCB.24.18.7965-7975.2004 }}</ref><ref name = pmid12511557>{{cite journal | vauthors = Mak BC, Takemaru K, Kenerson HL, Moon RT, Yeung RS | title = The tuberin-hamartin complex negatively regulates beta-catenin signaling activity | journal = The Journal of Biological Chemistry | volume = 278 | issue = 8 | pages = 5947–51 | date = February 2003 | pmid = 12511557 | doi = 10.1074/jbc.C200473200 }}</ref><ref name = pmid15851026>{{cite journal | vauthors = Ma L, Chen Z, Erdjument-Bromage H, Tempst P, Pandolfi PP | title = Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis | journal = Cell | volume = 121 | issue = 2 | pages = 179–93 | date = April 2005 | pmid = 15851026 | doi = 10.1016/j.cell.2005.02.031 }}</ref><ref name = pmid16636147>{{cite journal | vauthors = Cai SL, Tee AR, Short JD, Bergeron JM, Kim J, Shen J, Guo R, Johnson CL, Kiguchi K, Walker CL | title = Activity of TSC2 is inhibited by AKT-mediated phosphorylation and membrane partitioning | journal = The Journal of Cell Biology | volume = 173 | issue = 2 | pages = 279–89 | date = April 2006 | pmid = 16636147 | pmc = 2063818 | doi = 10.1083/jcb.200507119 }}</ref><ref name = pmid17077083>{{cite journal | vauthors = Cao Y, Kamioka Y, Yokoi N, Kobayashi T, Hino O, Onodera M, Mochizuki N, Nakae J | title = Interaction of FoxO1 and TSC2 induces insulin resistance through activation of the mammalian target of rapamycin/p70 S6K pathway | journal = The Journal of Biological Chemistry | volume = 281 | issue = 52 | pages = 40242–51 | date = December 2006 | pmid = 17077083 | doi = 10.1074/jbc.M608116200 }}</ref><ref name = pmid14651849>{{cite journal | vauthors = Inoki K, Zhu T, Guan KL | title = TSC2 mediates cellular energy response to control cell growth and survival | journal = Cell | volume = 115 | issue = 5 | pages = 577–90 | date = November 2003 | pmid = 14651849 | doi = 10.1016/S0092-8674(03)00929-2 }}</ref><ref name = pmid15963462>{{cite journal | vauthors = Nellist M, Burgers PC, van den Ouweland AM, Halley DJ, Luider TM | title = Phosphorylation and binding partner analysis of the TSC1-TSC2 complex | journal = Biochemical and Biophysical Research Communications | volume = 333 | issue = 3 | pages = 818–26 | date = August 2005 | pmid = 15963462 | doi = 10.1016/j.bbrc.2005.05.175 }}</ref><ref name = pmid16424383>{{cite journal | vauthors = Goncharova EA, Goncharov DA, Spaits M, Noonan DJ, Talovskaya E, Eszterhas A, Krymskaya VP | title = Abnormal growth of smooth muscle-like cells in lymphangioleiomyomatosis: Role for tumor suppressor TSC2 | journal = American Journal of Respiratory Cell and Molecular Biology | volume = 34 | issue = 5 | pages = 561–72 | date = May 2006 | pmid = 16424383 | pmc = 2644221 | doi = 10.1165/rcmb.2005-0300OC }}</ref><ref name = pmid14551205>{{cite journal | vauthors = Astrinidis A, Senapedis W, Coleman TR, Henske EP | title = Cell cycle-regulated phosphorylation of hamartin, the product of the tuberous sclerosis complex 1 gene, by cyclin-dependent kinase 1/cyclin B | journal = The Journal of Biological Chemistry | volume = 278 | issue = 51 | pages = 51372–9 | date = December 2003 | pmid = 14551205 | doi = 10.1074/jbc.M303956200 }}</ref><ref name = pmid11741832>{{cite journal | vauthors = Nellist M, Verhaaf B, Goedbloed MA, Reuser AJ, van den Ouweland AM, Halley DJ | title = TSC2 missense mutations inhibit tuberin phosphorylation and prevent formation of the tuberin-hamartin complex | journal = Human Molecular Genetics | volume = 10 | issue = 25 | pages = 2889–98 | date = December 2001 | pmid = 11741832 | doi = 10.1093/hmg/10.25.2889 }}</ref><ref name = pmid11175345>{{cite journal | vauthors = Benvenuto G, Li S, Brown SJ, Braverman R, Vass WC, Cheadle JP, Halley DJ, Sampson JR, Wienecke R, DeClue JE | title = The tuberous sclerosis-1 (TSC1) gene product hamartin suppresses cell growth and augments the expression of the TSC2 product tuberin by inhibiting its ubiquitination | journal = Oncogene | volume = 19 | issue = 54 | pages = 6306–16 | date = December 2000 | pmid = 11175345 | doi = 10.1038/sj.onc.1204009 }}</ref><ref name = pmid10807585>{{cite journal | vauthors = Murthy V, Haddad LA, Smith N, Pinney D, Tyszkowski R, Brown D, Ramesh V | title = Similarities and differences in the subcellular localization of hamartin and tuberin in the kidney | journal = American Journal of Physiology. Renal Physiology | volume = 278 | issue = 5 | pages = F737-46 | date = May 2000 | pmid = 10807585 | doi = 10.1152/ajprenal.2000.278.5.F737 }}</ref><ref name = pmid10915759>{{cite journal | vauthors = Miloloza A, Rosner M, Nellist M, Halley D, Bernaschek G, Hengstschläger M | title = The TSC1 gene product, hamartin, negatively regulates cell proliferation | journal = Human Molecular Genetics | volume = 9 | issue = 12 | pages = 1721–7 | date = July 2000 | pmid = 10915759 | doi = 10.1093/hmg/9.12.1721 }}</ref>


== See also ==
== See also ==
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==References==
== References ==
{{Reflist|35em}}
{{Reflist|35em}}


==Further reading==
== Further reading ==
{{Refbegin|35em}}
{{Refbegin|35em}}
*{{cite journal | author=Hengstschläger M |title=Tuberous sclerosis complex genes: from flies to human genetics. |journal=Arch. Dermatol. Res. |volume=293 |issue= 8 |pages= 383–6 |year= 2002 |pmid= 11686512 |doi=10.1007/s004030100250 }}
* {{cite journal | vauthors = Hengstschläger M | title = Tuberous sclerosis complex genes: from flies to human genetics | journal = Archives of Dermatological Research | volume = 293 | issue = 8 | pages = 383–6 | date = August 2001 | pmid = 11686512 | doi = 10.1007/s004030100250 }}
*{{cite journal | author=Ramesh V |title=Aspects of tuberous sclerosis complex (TSC) protein function in the brain. |journal=Biochem. Soc. Trans. |volume=31 |issue= Pt 3 |pages= 579–83 |year= 2004 |pmid= 12773159 |doi=10.1042/BST0310579 }}
* {{cite journal | vauthors = Ramesh V | title = Aspects of tuberous sclerosis complex (TSC) protein function in the brain | journal = Biochemical Society Transactions | volume = 31 | issue = Pt 3 | pages = 579–83 | date = June 2003 | pmid = 12773159 | doi = 10.1042/BST0310579 }}
*{{cite journal | vauthors=Knowles MA, Hornigold N, Pitt E |title=Tuberous sclerosis complex (TSC) gene involvement in sporadic tumours. |journal=Biochem. Soc. Trans. |volume=31 |issue= Pt 3 |pages= 597–602 |year= 2004 |pmid= 12773163 |doi=10.1042/BST0310597 }}
* {{cite journal | vauthors = Knowles MA, Hornigold N, Pitt E | title = Tuberous sclerosis complex (TSC) gene involvement in sporadic tumours | journal = Biochemical Society Transactions | volume = 31 | issue = Pt 3 | pages = 597–602 | date = June 2003 | pmid = 12773163 | doi = 10.1042/BST0310597 }}
*{{cite journal | author=Ellisen LW |title=Growth control under stress: mTOR regulation through the REDD1-TSC pathway. |journal=Cell Cycle |volume=4 |issue= 11 |pages= 1500–02 |year= 2007 |pmid= 16258273 |doi=10.4161/cc.4.11.2139 }}
* {{cite journal | vauthors = Ellisen LW | title = Growth control under stress: mTOR regulation through the REDD1-TSC pathway | journal = Cell Cycle | volume = 4 | issue = 11 | pages = 1500–02 | date = November 2005 | pmid = 16258273 | doi = 10.4161/cc.4.11.2139 }}
*{{cite journal | vauthors=Jozwiak J, Jozwiak S |title=Giant cells: contradiction to two-hit model of tuber formation? |journal=Cell. Mol. Neurobiol. |volume=27 |issue= 2 |pages= 251–61 |year= 2007 |pmid= 16897363 |doi= 10.1007/s10571-006-9106-0 }}
* {{cite journal | vauthors = Jozwiak J, Jozwiak S | title = Giant cells: contradiction to two-hit model of tuber formation? | journal = Cellular and Molecular Neurobiology | volume = 27 | issue = 2 | pages = 251–61 | date = March 2007 | pmid = 16897363 | doi = 10.1007/s10571-006-9106-0 }}
*{{cite journal   |vauthors=Nagase T, Seki N, Ishikawa K, etal |title=Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain. |journal=DNA Res. |volume=3 |issue= 5 |pages= 321–9, 341–54 |year= 1997 |pmid= 9039502 |doi=10.1093/dnares/3.5.321 }}
* {{cite journal | vauthors = Nagase T, Seki N, Ishikawa K, Ohira M, Kawarabayasi Y, Ohara O, Tanaka A, Kotani H, Miyajima N, Nomura N | title = Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain | journal = DNA Research | volume = 3 | issue = 5 | pages = 321–9, 341-54 | date = October 1996 | pmid = 9039502 | doi = 10.1093/dnares/3.5.321 }}
*{{cite journal   |vauthors=van Slegtenhorst M, de Hoogt R, Hermans C, etal |title=Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. |journal=Science |volume=277 |issue= 5327 |pages= 805–8 |year= 1997 |pmid= 9242607 |doi=10.1126/science.277.5327.805  }}
* {{cite journal | vauthors = van Slegtenhorst M, de Hoogt R, Hermans C, Nellist M, Janssen B, Verhoef S, Lindhout D, van den Ouweland A, Halley D, Young J, Burley M, Jeremiah S, Woodward K, Nahmias J, Fox M, Ekong R, Osborne J, Wolfe J, Povey S, Snell RG, Cheadle JP, Jones AC, Tachataki M, Ravine D, Sampson JR, Reeve MP, Richardson P, Wilmer F, Munro C, Hawkins TL, Sepp T, Ali JB, Ward S, Green AJ, Yates JR, Kwiatkowska J, Henske EP, Short MP, Haines JH, Jozwiak S, Kwiatkowski DJ | title = Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34 | journal = Science | volume = 277 | issue = 5327 | pages = 805–8 | date = August 1997 | pmid = 9242607 | doi = 10.1126/science.277.5327.805 }}
*{{cite journal  |vauthors=Jones AC, Daniells CE, Snell RG, etal |title=Molecular genetic and phenotypic analysis reveals differences between TSC1 and TSC2 associated familial and sporadic tuberous sclerosis. |journal=Hum. Mol. Genet. |volume=6 |issue= 12 |pages= 2155–61 |year= 1997 |pmid= 9328481 |doi=10.1093/hmg/6.12.2155  }}
* {{cite journal | vauthors = Jones AC, Daniells CE, Snell RG, Tachataki M, Idziaszczyk SA, Krawczak M, Sampson JR, Cheadle JP | title = Molecular genetic and phenotypic analysis reveals differences between TSC1 and TSC2 associated familial and sporadic tuberous sclerosis | journal = Human Molecular Genetics | volume = 6 | issue = 12 | pages = 2155–61 | date = November 1997 | pmid = 9328481 | doi = 10.1093/hmg/6.12.2155 }}
*{{cite journal   |vauthors=van Slegtenhorst M, Nellist M, Nagelkerken B, etal |title=Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products. |journal=Hum. Mol. Genet. |volume=7 |issue= 6 |pages= 1053–7 |year= 1998 |pmid= 9580671 |doi=10.1093/hmg/7.6.1053  }}
* {{cite journal | vauthors = van Slegtenhorst M, Nellist M, Nagelkerken B, Cheadle J, Snell R, van den Ouweland A, Reuser A, Sampson J, Halley D, van der Sluijs P | title = Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products | journal = Human Molecular Genetics | volume = 7 | issue = 6 | pages = 1053–7 | date = June 1998 | pmid = 9580671 | doi = 10.1093/hmg/7.6.1053 }}
*{{cite journal | vauthors=Plank TL, Yeung RS, Henske EP |title=Hamartin, the product of the tuberous sclerosis 1 (TSC1) gene, interacts with tuberin and appears to be localized to cytoplasmic vesicles. |journal=Cancer Res. |volume=58 |issue= 21 |pages= 4766–70 |year= 1998 |pmid= 9809973 |doi= }}
* {{cite journal | vauthors = Plank TL, Yeung RS, Henske EP | title = Hamartin, the product of the tuberous sclerosis 1 (TSC1) gene, interacts with tuberin and appears to be localized to cytoplasmic vesicles | journal = Cancer Research | volume = 58 | issue = 21 | pages = 4766–70 | date = November 1998 | pmid = 9809973 | doi = }}
*{{cite journal   |vauthors=Kwiatkowska J, Jozwiak S, Hall F, etal |title=Comprehensive mutational analysis of the TSC1 gene: observations on frequency of mutation, associated features, and nonpenetrance. |journal=Ann. Hum. Genet. |volume=62 |issue= Pt 4 |pages= 277–85 |year= 1999 |pmid= 9924605 |doi= 10.1046/j.1469-1809.1998.6240277.x }}
* {{cite journal | vauthors = Kwiatkowska J, Jozwiak S, Hall F, Henske EP, Haines JL, McNamara P, Braiser J, Wigowska-Sowinska J, Kasprzyk-Obara J, Short MP, Kwiatkowski DJ | title = Comprehensive mutational analysis of the TSC1 gene: observations on frequency of mutation, associated features, and nonpenetrance | journal = Annals of Human Genetics | volume = 62 | issue = Pt 4 | pages = 277–85 | date = July 1998 | pmid = 9924605 | doi = 10.1046/j.1469-1809.1998.6240277.x }}
*{{cite journal   |vauthors=van Slegtenhorst M, Verhoef S, Tempelaars A, etal |title=Mutational spectrum of the TSC1 gene in a cohort of 225 tuberous sclerosis complex patients: no evidence for genotype-phenotype correlation. |journal=J. Med. Genet. |volume=36 |issue= 4 |pages= 285–9 |year= 1999 |pmid= 10227394 |doi= 10.1136/jmg.36.4.285 | pmc=1734341  }}
* {{cite journal | vauthors = van Slegtenhorst M, Verhoef S, Tempelaars A, Bakker L, Wang Q, Wessels M, Bakker R, Nellist M, Lindhout D, Halley D, van den Ouweland A | title = Mutational spectrum of the TSC1 gene in a cohort of 225 tuberous sclerosis complex patients: no evidence for genotype-phenotype correlation | journal = Journal of Medical Genetics | volume = 36 | issue = 4 | pages = 285–9 | date = April 1999 | pmid = 10227394 | pmc = 1734341 | doi = 10.1136/jmg.36.4.285 }}
*{{cite journal   |vauthors=Niida Y, Lawrence-Smith N, Banwell A, etal |title=Analysis of both TSC1 and TSC2 for germline mutations in 126 unrelated patients with tuberous sclerosis. |journal=Hum. Mutat. |volume=14 |issue= 5 |pages= 412–22 |year= 2000 |pmid= 10533067 |doi= 10.1002/(SICI)1098-1004(199911)14:5<412::AID-HUMU7>3.0.CO;2-K }}
* {{cite journal | vauthors = Niida Y, Lawrence-Smith N, Banwell A, Hammer E, Lewis J, Beauchamp RL, Sims K, Ramesh V, Ozelius L | title = Analysis of both TSC1 and TSC2 for germline mutations in 126 unrelated patients with tuberous sclerosis | journal = Human Mutation | volume = 14 | issue = 5 | pages = 412–22 | year = 2000 | pmid = 10533067 | doi = 10.1002/(SICI)1098-1004(199911)14:5<412::AID-HUMU7>3.0.CO;2-K }}
*{{cite journal   |vauthors=Zhang H, Nanba E, Yamamoto T, etal |title=Mutational analysis of TSC1 and TSC2 genes in Japanese patients with tuberous sclerosis complex. |journal=J. Hum. Genet. |volume=44 |issue= 6 |pages= 391–6 |year= 2000 |pmid= 10570911 |doi=10.1007/s100380050185  }}
* {{cite journal | vauthors = Zhang H, Nanba E, Yamamoto T, Ninomiya H, Ohno K, Mizuguchi M, Takeshita K | title = Mutational analysis of TSC1 and TSC2 genes in Japanese patients with tuberous sclerosis complex | journal = Journal of Human Genetics | volume = 44 | issue = 6 | pages = 391–6 | year = 2000 | pmid = 10570911 | doi = 10.1007/s100380050185 }}
*{{cite journal  |vauthors=Nellist M, van Slegtenhorst MA, Goedbloed M, etal |title=Characterization of the cytosolic tuberin-hamartin complex. Tuberin is a cytosolic chaperone for hamartin. |journal=J. Biol. Chem. |volume=274 |issue= 50 |pages= 35647–52 |year= 2000 |pmid= 10585443 |doi=10.1074/jbc.274.50.35647  }}
* {{cite journal | vauthors = Nellist M, van Slegtenhorst MA, Goedbloed M, van den Ouweland AM, Halley DJ, van der Sluijs P | title = Characterization of the cytosolic tuberin-hamartin complex. Tuberin is a cytosolic chaperone for hamartin | journal = The Journal of Biological Chemistry | volume = 274 | issue = 50 | pages = 35647–52 | date = December 1999 | pmid = 10585443 | doi = 10.1074/jbc.274.50.35647 }}
*{{cite journal   |vauthors=Yamashita Y, Ono J, Okada S, etal |title=Analysis of all exons of TSC1 and TSC2 genes for germline mutations in Japanese patients with tuberous sclerosis: report of 10 mutations. |journal=Am. J. Med. Genet. |volume=90 |issue= 2 |pages= 123–6 |year= 2000 |pmid= 10607950 |doi=10.1002/(SICI)1096-8628(20000117)90:2<123::AID-AJMG7>3.0.CO;2-L  }}
* {{cite journal | vauthors = Yamashita Y, Ono J, Okada S, Wataya-Kaneda M, Yoshikawa K, Nishizawa M, Hirayama Y, Kobayashi E, Seyama K, Hino O | title = Analysis of all exons of TSC1 and TSC2 genes for germline mutations in Japanese patients with tuberous sclerosis: report of 10 mutations | journal = American Journal of Medical Genetics | volume = 90 | issue = 2 | pages = 123–6 | date = January 2000 | pmid = 10607950 | doi = 10.1002/(SICI)1096-8628(20000117)90:2<123::AID-AJMG7>3.0.CO;2-L }}
*{{cite journal   |vauthors=Lamb RF, Roy C, Diefenbach TJ, etal |title=The TSC1 tumour suppressor hamartin regulates cell adhesion through ERM proteins and the GTPase Rho. |journal=Nat. Cell Biol. |volume=2 |issue= 5 |pages= 281–7 |year= 2000 |pmid= 10806479 |doi= 10.1038/35010550 }}
* {{cite journal | vauthors = Lamb RF, Roy C, Diefenbach TJ, Vinters HV, Johnson MW, Jay DG, Hall A | title = The TSC1 tumour suppressor hamartin regulates cell adhesion through ERM proteins and the GTPase Rho | journal = Nature Cell Biology | volume = 2 | issue = 5 | pages = 281–7 | date = May 2000 | pmid = 10806479 | doi = 10.1038/35010550 }}
*{{cite journal  |vauthors=Miloloza A, Rosner M, Nellist M, etal |title=The TSC1 gene product, hamartin, negatively regulates cell proliferation. |journal=Hum. Mol. Genet. |volume=9 |issue= 12 |pages= 1721–7 |year= 2000 |pmid= 10915759 |doi=10.1093/hmg/9.12.1721  }}
* {{cite journal | vauthors = Miloloza A, Rosner M, Nellist M, Halley D, Bernaschek G, Hengstschläger M | title = The TSC1 gene product, hamartin, negatively regulates cell proliferation | journal = Human Molecular Genetics | volume = 9 | issue = 12 | pages = 1721–7 | date = July 2000 | pmid = 10915759 | doi = 10.1093/hmg/9.12.1721 }}
*{{cite journal   |vauthors=Murthy V, Stemmer-Rachamimov AO, Haddad LA, etal |title=Developmental expression of the tuberous sclerosis proteins tuberin and hamartin. |journal=Acta Neuropathol. |volume=101 |issue= 3 |pages= 202–10 |year= 2001 |pmid= 11307618 |doi= 10.1007/s004010000269}}
* {{cite journal | vauthors = Murthy V, Stemmer-Rachamimov AO, Haddad LA, Roy JE, Cutone AN, Beauchamp RL, Smith N, Louis DN, Ramesh V | title = Developmental expression of the tuberous sclerosis proteins tuberin and hamartin | journal = Acta Neuropathologica | volume = 101 | issue = 3 | pages = 202–10 | date = March 2001 | pmid = 11307618 | doi = 10.1007/s004010000269 }}
*{{cite journal  | vauthors=Catania MG, Mischel PS, Vinters HV |title=Hamartin and tuberin interaction with the G2/M cyclin-dependent kinase CDK1 and its regulatory cyclins A and B. |journal=J. Neuropathol. Exp. Neurol. |volume=60 |issue= 7 |pages= 711–23 |year= 2001 |pmid= 11444800 |doi=  }}
* {{cite journal | vauthors = Catania MG, Mischel PS, Vinters HV | title = Hamartin and tuberin interaction with the G2/M cyclin-dependent kinase CDK1 and its regulatory cyclins A and B | journal = Journal of Neuropathology and Experimental Neurology | volume = 60 | issue = 7 | pages = 711–23 | date = July 2001 | pmid = 11444800 | doi =  }}
{{Refend}}
{{Refend}}


==External links==
== External links ==
* [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=tuberous-sclerosis  GeneReviews/NIH/NCBI/UW entry on Tuberous Sclerosis Complex or Bourneville Disease]
* [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=tuberous-sclerosis  GeneReviews/NIH/NCBI/UW entry on Tuberous Sclerosis Complex or Bourneville Disease]


{{GTP-binding protein regulators}}
{{GTP-binding protein regulators}}

Latest revision as of 07:31, 10 January 2019

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
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View/Edit Human

Tuberous sclerosis 1 (TSC1), also known as Hamartin, is a protein that in humans is encoded by the TSC1 gene.[1]

Function

TSC1 functions as a co-chaperone which inhibits the ATPase activity of the chaperone Hsp90 (heat shock protein-90) and decelerates its chaperone cycle. Tsc1 functions as a facilitator of Hsp90 in chaperoning the kinase and non-kinase clients including Tsc2, therefore preventing their ubiquitination and degradation in the proteasome.[2] TSC1, TSC2 and TBC1D7 is a multi-protein complex also known as the TSC complex. This complex negatively regulates mTORC1 signaling by functioning as a GTPase-activating protein (GAP) for the small GTPase Rheb, an essential activator of mTORC1. The TSC complex has been implicated as a tumor suppressor.

Clinical significance

Defects in this gene can cause tuberous sclerosis, due to a functional impairment of the TSC complex.[citation needed] Defects in TSC1 may also be a cause of focal cortical dysplasia.[citation needed] TSC1 may be involved in protecting brain neurons in the CA3 region of the hippocampus from the effects of stroke.[3]

Interactions

TSC1 has been shown to interact with:

See also

References

  1. ↑ "Entrez Gene: TSC1 tuberous sclerosis 1".
  2. ↑ 2.0 2.1 2.2 Woodford MR, Sager RA, Marris E, Dunn DM, Blanden AR, Murphy RL, Rensing N, Shapiro O, Panaretou B, Prodromou C, Loh SN, Gutmann DH, Bourboulia D, Bratslavsky G, Wong M, Mollapour M (December 2017). "Tumor suppressor Tsc1 is a new Hsp90 co-chaperone that facilitates folding of kinase and non-kinase clients". The EMBO Journal. 36 (24): 3650–3665. doi:10.15252/embj.201796700. PMC 5730846. PMID 29127155.
  3. ↑ Papadakis M, Hadley G, Xilouri M, Hoyte LC, Nagel S, McMenamin MM, Tsaknakis G, Watt SM, Drakesmith CW, Chen R, Wood MJ, Zhao Z, Kessler B, Vekrellis K, Buchan AM (March 2013). "Tsc1 (hamartin) confers neuroprotection against ischemia by inducing autophagy". Nature Medicine. 19 (3): 351–7. doi:10.1038/nm.3097. PMC 3744134. PMID 23435171.
  4. ↑ Roux PP, Ballif BA, Anjum R, Gygi SP, Blenis J (September 2004). "Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase". Proceedings of the National Academy of Sciences of the United States of America. 101 (37): 13489–94. doi:10.1073/pnas.0405659101. PMC 518784. PMID 15342917.
  5. ↑ 5.0 5.1 Dan HC, Sun M, Yang L, Feldman RI, Sui XM, Ou CC, Nellist M, Yeung RS, Halley DJ, Nicosia SV, Pledger WJ, Cheng JQ (September 2002). "Phosphatidylinositol 3-kinase/Akt pathway regulates tuberous sclerosis tumor suppressor complex by phosphorylation of tuberin". The Journal of Biological Chemistry. 277 (38): 35364–70. doi:10.1074/jbc.M205838200. PMID 12167664.
  6. ↑ Haddad LA, Smith N, Bowser M, Niida Y, Murthy V, Gonzalez-Agosti C, Ramesh V (November 2002). "The TSC1 tumor suppressor hamartin interacts with neurofilament-L and possibly functions as a novel integrator of the neuronal cytoskeleton". The Journal of Biological Chemistry. 277 (46): 44180–6. doi:10.1074/jbc.M207211200. PMID 12226091.
  7. ↑ 7.0 7.1 Astrinidis A, Senapedis W, Henske EP (January 2006). "Hamartin, the tuberous sclerosis complex 1 gene product, interacts with polo-like kinase 1 in a phosphorylation-dependent manner". Human Molecular Genetics. 15 (2): 287–97. doi:10.1093/hmg/ddi444. PMID 16339216.
  8. ↑ Hodges AK, Li S, Maynard J, Parry L, Braverman R, Cheadle JP, DeClue JE, Sampson JR (December 2001). "Pathological mutations in TSC1 and TSC2 disrupt the interaction between hamartin and tuberin". Human Molecular Genetics. 10 (25): 2899–905. doi:10.1093/hmg/10.25.2899. PMID 11741833.
  9. ↑ Aicher LD, Campbell JS, Yeung RS (June 2001). "Tuberin phosphorylation regulates its interaction with hamartin. Two proteins involved in tuberous sclerosis". The Journal of Biological Chemistry. 276 (24): 21017–21. doi:10.1074/jbc.C100136200. PMID 11290735.
  10. ↑ van Slegtenhorst M, Nellist M, Nagelkerken B, Cheadle J, Snell R, van den Ouweland A, Reuser A, Sampson J, Halley D, van der Sluijs P (June 1998). "Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products". Human Molecular Genetics. 7 (6): 1053–7. doi:10.1093/hmg/7.6.1053. PMID 9580671.
  11. ↑ Nellist M, Goedbloed MA, de Winter C, Verhaaf B, Jankie A, Reuser AJ, van den Ouweland AM, van der Sluijs P, Halley DJ (October 2002). "Identification and characterization of the interaction between tuberin and 14-3-3zeta". The Journal of Biological Chemistry. 277 (42): 39417–24. doi:10.1074/jbc.M204802200. PMID 12176984.
  12. ↑ Li Y, Inoki K, Guan KL (September 2004). "Biochemical and functional characterizations of small GTPase Rheb and TSC2 GAP activity". Molecular and Cellular Biology. 24 (18): 7965–75. doi:10.1128/MCB.24.18.7965-7975.2004. PMC 515062. PMID 15340059.
  13. ↑ Mak BC, Takemaru K, Kenerson HL, Moon RT, Yeung RS (February 2003). "The tuberin-hamartin complex negatively regulates beta-catenin signaling activity". The Journal of Biological Chemistry. 278 (8): 5947–51. doi:10.1074/jbc.C200473200. PMID 12511557.
  14. ↑ Ma L, Chen Z, Erdjument-Bromage H, Tempst P, Pandolfi PP (April 2005). "Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis". Cell. 121 (2): 179–93. doi:10.1016/j.cell.2005.02.031. PMID 15851026.
  15. ↑ Cai SL, Tee AR, Short JD, Bergeron JM, Kim J, Shen J, Guo R, Johnson CL, Kiguchi K, Walker CL (April 2006). "Activity of TSC2 is inhibited by AKT-mediated phosphorylation and membrane partitioning". The Journal of Cell Biology. 173 (2): 279–89. doi:10.1083/jcb.200507119. PMC 2063818. PMID 16636147.
  16. ↑ Cao Y, Kamioka Y, Yokoi N, Kobayashi T, Hino O, Onodera M, Mochizuki N, Nakae J (December 2006). "Interaction of FoxO1 and TSC2 induces insulin resistance through activation of the mammalian target of rapamycin/p70 S6K pathway". The Journal of Biological Chemistry. 281 (52): 40242–51. doi:10.1074/jbc.M608116200. PMID 17077083.
  17. ↑ Inoki K, Zhu T, Guan KL (November 2003). "TSC2 mediates cellular energy response to control cell growth and survival". Cell. 115 (5): 577–90. doi:10.1016/S0092-8674(03)00929-2. PMID 14651849.
  18. ↑ Nellist M, Burgers PC, van den Ouweland AM, Halley DJ, Luider TM (August 2005). "Phosphorylation and binding partner analysis of the TSC1-TSC2 complex". Biochemical and Biophysical Research Communications. 333 (3): 818–26. doi:10.1016/j.bbrc.2005.05.175. PMID 15963462.
  19. ↑ Goncharova EA, Goncharov DA, Spaits M, Noonan DJ, Talovskaya E, Eszterhas A, Krymskaya VP (May 2006). "Abnormal growth of smooth muscle-like cells in lymphangioleiomyomatosis: Role for tumor suppressor TSC2". American Journal of Respiratory Cell and Molecular Biology. 34 (5): 561–72. doi:10.1165/rcmb.2005-0300OC. PMC 2644221. PMID 16424383.
  20. ↑ Astrinidis A, Senapedis W, Coleman TR, Henske EP (December 2003). "Cell cycle-regulated phosphorylation of hamartin, the product of the tuberous sclerosis complex 1 gene, by cyclin-dependent kinase 1/cyclin B". The Journal of Biological Chemistry. 278 (51): 51372–9. doi:10.1074/jbc.M303956200. PMID 14551205.
  21. ↑ Nellist M, Verhaaf B, Goedbloed MA, Reuser AJ, van den Ouweland AM, Halley DJ (December 2001). "TSC2 missense mutations inhibit tuberin phosphorylation and prevent formation of the tuberin-hamartin complex". Human Molecular Genetics. 10 (25): 2889–98. doi:10.1093/hmg/10.25.2889. PMID 11741832.
  22. ↑ Benvenuto G, Li S, Brown SJ, Braverman R, Vass WC, Cheadle JP, Halley DJ, Sampson JR, Wienecke R, DeClue JE (December 2000). "The tuberous sclerosis-1 (TSC1) gene product hamartin suppresses cell growth and augments the expression of the TSC2 product tuberin by inhibiting its ubiquitination". Oncogene. 19 (54): 6306–16. doi:10.1038/sj.onc.1204009. PMID 11175345.
  23. ↑ Murthy V, Haddad LA, Smith N, Pinney D, Tyszkowski R, Brown D, Ramesh V (May 2000). "Similarities and differences in the subcellular localization of hamartin and tuberin in the kidney". American Journal of Physiology. Renal Physiology. 278 (5): F737–46. doi:10.1152/ajprenal.2000.278.5.F737. PMID 10807585.
  24. ↑ Miloloza A, Rosner M, Nellist M, Halley D, Bernaschek G, Hengstschläger M (July 2000). "The TSC1 gene product, hamartin, negatively regulates cell proliferation". Human Molecular Genetics. 9 (12): 1721–7. doi:10.1093/hmg/9.12.1721. PMID 10915759.

Further reading

  • Hengstschläger M (August 2001). "Tuberous sclerosis complex genes: from flies to human genetics". Archives of Dermatological Research. 293 (8): 383–6. doi:10.1007/s004030100250. PMID 11686512.
  • Ramesh V (June 2003). "Aspects of tuberous sclerosis complex (TSC) protein function in the brain". Biochemical Society Transactions. 31 (Pt 3): 579–83. doi:10.1042/BST0310579. PMID 12773159.
  • Knowles MA, Hornigold N, Pitt E (June 2003). "Tuberous sclerosis complex (TSC) gene involvement in sporadic tumours". Biochemical Society Transactions. 31 (Pt 3): 597–602. doi:10.1042/BST0310597. PMID 12773163.
  • Ellisen LW (November 2005). "Growth control under stress: mTOR regulation through the REDD1-TSC pathway". Cell Cycle. 4 (11): 1500–02. doi:10.4161/cc.4.11.2139. PMID 16258273.
  • Jozwiak J, Jozwiak S (March 2007). "Giant cells: contradiction to two-hit model of tuber formation?". Cellular and Molecular Neurobiology. 27 (2): 251–61. doi:10.1007/s10571-006-9106-0. PMID 16897363.
  • Nagase T, Seki N, Ishikawa K, Ohira M, Kawarabayasi Y, Ohara O, Tanaka A, Kotani H, Miyajima N, Nomura N (October 1996). "Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain". DNA Research. 3 (5): 321–9, 341–54. doi:10.1093/dnares/3.5.321. PMID 9039502.
  • van Slegtenhorst M, de Hoogt R, Hermans C, Nellist M, Janssen B, Verhoef S, Lindhout D, van den Ouweland A, Halley D, Young J, Burley M, Jeremiah S, Woodward K, Nahmias J, Fox M, Ekong R, Osborne J, Wolfe J, Povey S, Snell RG, Cheadle JP, Jones AC, Tachataki M, Ravine D, Sampson JR, Reeve MP, Richardson P, Wilmer F, Munro C, Hawkins TL, Sepp T, Ali JB, Ward S, Green AJ, Yates JR, Kwiatkowska J, Henske EP, Short MP, Haines JH, Jozwiak S, Kwiatkowski DJ (August 1997). "Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34". Science. 277 (5327): 805–8. doi:10.1126/science.277.5327.805. PMID 9242607.
  • Jones AC, Daniells CE, Snell RG, Tachataki M, Idziaszczyk SA, Krawczak M, Sampson JR, Cheadle JP (November 1997). "Molecular genetic and phenotypic analysis reveals differences between TSC1 and TSC2 associated familial and sporadic tuberous sclerosis". Human Molecular Genetics. 6 (12): 2155–61. doi:10.1093/hmg/6.12.2155. PMID 9328481.
  • van Slegtenhorst M, Nellist M, Nagelkerken B, Cheadle J, Snell R, van den Ouweland A, Reuser A, Sampson J, Halley D, van der Sluijs P (June 1998). "Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products". Human Molecular Genetics. 7 (6): 1053–7. doi:10.1093/hmg/7.6.1053. PMID 9580671.
  • Plank TL, Yeung RS, Henske EP (November 1998). "Hamartin, the product of the tuberous sclerosis 1 (TSC1) gene, interacts with tuberin and appears to be localized to cytoplasmic vesicles". Cancer Research. 58 (21): 4766–70. PMID 9809973.
  • Kwiatkowska J, Jozwiak S, Hall F, Henske EP, Haines JL, McNamara P, Braiser J, Wigowska-Sowinska J, Kasprzyk-Obara J, Short MP, Kwiatkowski DJ (July 1998). "Comprehensive mutational analysis of the TSC1 gene: observations on frequency of mutation, associated features, and nonpenetrance". Annals of Human Genetics. 62 (Pt 4): 277–85. doi:10.1046/j.1469-1809.1998.6240277.x. PMID 9924605.
  • van Slegtenhorst M, Verhoef S, Tempelaars A, Bakker L, Wang Q, Wessels M, Bakker R, Nellist M, Lindhout D, Halley D, van den Ouweland A (April 1999). "Mutational spectrum of the TSC1 gene in a cohort of 225 tuberous sclerosis complex patients: no evidence for genotype-phenotype correlation". Journal of Medical Genetics. 36 (4): 285–9. doi:10.1136/jmg.36.4.285. PMC 1734341. PMID 10227394.
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External links

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