LATS1: Difference between revisions
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''' | '''Large tumor suppressor kinase 1 (LATS1)''' is an [[enzyme]] that in humans is encoded by the ''LATS1'' [[gene]].<ref name="pmid9988268">{{cite journal |vauthors=Tao W, Zhang S, Turenchalk GS, Stewart RA, St John MA, Chen W, Xu T | title = Human homologue of the Drosophila melanogaster lats tumour suppressor modulates CDC2 activity | journal = Nat Genet | volume = 21 | issue = 2 | pages = 177–81 |date=February 1999 | pmid = 9988268 | pmc = | doi = 10.1038/5960 }}</ref><ref name="pmid15122335">{{cite journal |vauthors=Iida S, Hirota T, Morisaki T, Marumoto T, Hara T, Kuninaka S, Honda S, Kosai K, Kawasuji M, Pallas DC, Saya H | title = Tumor suppressor WARTS ensures genomic integrity by regulating both mitotic progression and G1 tetraploidy checkpoint function | journal = Oncogene | volume = 23 | issue = 31 | pages = 5266–74 |date=July 2004 | pmid = 15122335 | pmc = | doi = 10.1038/sj.onc.1207623 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: LATS1 LATS, large tumor suppressor, homolog 1 (Drosophila)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9113| accessdate = }}</ref> | ||
It has been associated with the [[Hippo signaling pathway]].<ref name="pmid18158288">{{cite journal |vauthors=Hao Y, Chun A, Cheung K, Rashidi B, Yang X |title=Tumor suppressor LATS1 is a negative regulator of oncogene YAP |journal=J. Biol. Chem. |volume=283 |issue=9 |pages=5496–509 |date=February 2008 |pmid=18158288 |doi=10.1074/jbc.M709037200 |url=http://www.jbc.org/cgi/pmidlookup?view=long&pmid=18158288}}</ref> | It has been associated with the [[Hippo signaling pathway]].<ref name="pmid18158288">{{cite journal |vauthors=Hao Y, Chun A, Cheung K, Rashidi B, Yang X |title=Tumor suppressor LATS1 is a negative regulator of oncogene YAP |journal=J. Biol. Chem. |volume=283 |issue=9 |pages=5496–509 |date=February 2008 |pmid=18158288 |doi=10.1074/jbc.M709037200 |url=http://www.jbc.org/cgi/pmidlookup?view=long&pmid=18158288}}</ref> | ||
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{{PBB_Summary | {{PBB_Summary | ||
| section_title = | | section_title = | ||
| summary_text = The protein encoded by this gene is a putative serine/threonine kinase that localizes to the mitotic apparatus and complexes with cell cycle controller CDC2 kinase in early mitosis. The protein is phosphorylated in a cell-cycle dependent manner, with late prophase phosphorylation remaining through metaphase. The N-terminal region of the protein binds CDC2 to form a complex showing reduced H1 | | summary_text = The protein encoded by this gene is a putative [[serine/threonine kinase]] that localizes to the [[mitotic apparatus]] and complexes with [[cell cycle]] controller [[CDC2]] kinase in early [[mitosis]]. The protein is [[phosphorylation|phosphorylated]] in a cell-cycle dependent manner, with late [[prophase]] phosphorylation remaining through [[metaphase]]. The [[N-terminal]] region of the protein binds CDC2 to form a complex showing reduced [[histone H1]] kinase activity, indicating a role as a negative regulator of CDC2/[[cyclin A]]. In addition, the [[C-terminal]] kinase domain binds to its own N-terminal region, suggesting potential [[negative regulation]] through interference with complex formation via intramolecular binding. Biochemical and genetic data suggest a role as a [[tumor suppressor]]. This is supported by studies in knockout mice showing development of [[soft-tissue sarcoma|soft-tissue sarcomas]], [[ovarian tumor|ovarian stromal cell tumors]] and a high sensitivity to [[carcinogen|carcinogenic]] treatments.<ref name="entrez"/> | ||
}} | }} | ||
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*{{cite journal |vauthors=Morisaki T, Hirota T, Iida S, etal |title=WARTS tumor suppressor is phosphorylated by Cdc2/cyclin B at spindle poles during mitosis. |journal=FEBS Lett. |volume=529 |issue= 2–3 |pages= 319–24 |year= 2002 |pmid= 12372621 |doi=10.1016/S0014-5793(02)03360-4 }} | *{{cite journal |vauthors=Morisaki T, Hirota T, Iida S, etal |title=WARTS tumor suppressor is phosphorylated by Cdc2/cyclin B at spindle poles during mitosis. |journal=FEBS Lett. |volume=529 |issue= 2–3 |pages= 319–24 |year= 2002 |pmid= 12372621 |doi=10.1016/S0014-5793(02)03360-4 }} | ||
*{{cite journal |vauthors=Hisaoka M, Tanaka A, Hashimoto H |title=Molecular alterations of h-warts/LATS1 tumor suppressor in human soft tissue sarcoma |journal=Lab. Invest. |volume=82 |issue= 10 |pages= 1427–35 |year= 2002 |pmid= 12379777 |doi= 10.1097/01.lab.0000032381.68634.ca}} | *{{cite journal |vauthors=Hisaoka M, Tanaka A, Hashimoto H |title=Molecular alterations of h-warts/LATS1 tumor suppressor in human soft tissue sarcoma |journal=Lab. Invest. |volume=82 |issue= 10 |pages= 1427–35 |year= 2002 |pmid= 12379777 |doi= 10.1097/01.lab.0000032381.68634.ca}} | ||
*{{cite journal |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 }} | *{{cite journal |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 |bibcode=2002PNAS...9916899M }} | ||
*{{cite journal |vauthors=Kamikubo Y, Takaori-Kondo A, Uchiyama T, Hori T |title=Inhibition of cell growth by conditional expression of kpm, a human homologue of Drosophila warts/lats tumor suppressor |journal=J. Biol. Chem. |volume=278 |issue= 20 |pages= 17609–14 |year= 2003 |pmid= 12624101 |doi= 10.1074/jbc.M211974200 }} | *{{cite journal |vauthors=Kamikubo Y, Takaori-Kondo A, Uchiyama T, Hori T |title=Inhibition of cell growth by conditional expression of kpm, a human homologue of Drosophila warts/lats tumor suppressor |journal=J. Biol. Chem. |volume=278 |issue= 20 |pages= 17609–14 |year= 2003 |pmid= 12624101 |doi= 10.1074/jbc.M211974200 }} | ||
*{{cite journal |vauthors=Brill LM, Salomon AR, Ficarro SB, etal |title=Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry |journal=Anal. Chem. |volume=76 |issue= 10 |pages= 2763–72 |year= 2004 |pmid= 15144186 |doi= 10.1021/ac035352d }} | *{{cite journal |vauthors=Brill LM, Salomon AR, Ficarro SB, etal |title=Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry |journal=Anal. Chem. |volume=76 |issue= 10 |pages= 2763–72 |year= 2004 |pmid= 15144186 |doi= 10.1021/ac035352d }} | ||
*{{cite journal |vauthors=Yang X, Yu K, Hao Y, etal |title=LATS1 tumour suppressor affects cytokinesis by inhibiting LIMK1 |journal=Nat. Cell Biol. |volume=6 |issue= 7 |pages= 609–17 |year= 2004 |pmid= 15220930 |doi= 10.1038/ncb1140 }} | *{{cite journal |vauthors=Yang X, Yu K, Hao Y, etal |title=LATS1 tumour suppressor affects cytokinesis by inhibiting LIMK1 |journal=Nat. Cell Biol. |volume=6 |issue= 7 |pages= 609–17 |year= 2004 |pmid= 15220930 |doi= 10.1038/ncb1140 }} | ||
*{{cite journal |vauthors=Beausoleil SA, Jedrychowski M, Schwartz D, etal |title=Large-scale characterization of HeLa cell nuclear phosphoproteins |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=101 |issue= 33 |pages= 12130–5 |year= 2004 |pmid= 15302935 |doi= 10.1073/pnas.0404720101 | pmc=514446 }} | *{{cite journal |vauthors=Beausoleil SA, Jedrychowski M, Schwartz D, etal |title=Large-scale characterization of HeLa cell nuclear phosphoproteins |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=101 |issue= 33 |pages= 12130–5 |year= 2004 |pmid= 15302935 |doi= 10.1073/pnas.0404720101 | pmc=514446 |bibcode=2004PNAS..10112130B }} | ||
*{{cite journal |vauthors=Gerhard DS, Wagner L, Feingold EA, etal |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 | pmc=528928 }} | *{{cite journal |vauthors=Gerhard DS, Wagner L, Feingold EA, etal |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 | pmc=528928 }} | ||
*{{cite journal |vauthors=Chan EH, Nousiainen M, Chalamalasetty RB, etal |title=The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1 |journal=Oncogene |volume=24 |issue= 12 |pages= 2076–86 |year= 2005 |pmid= 15688006 |doi= 10.1038/sj.onc.1208445 }} | *{{cite journal |vauthors=Chan EH, Nousiainen M, Chalamalasetty RB, etal |title=The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1 |journal=Oncogene |volume=24 |issue= 12 |pages= 2076–86 |year= 2005 |pmid= 15688006 |doi= 10.1038/sj.onc.1208445 }} |
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Large tumor suppressor kinase 1 (LATS1) is an enzyme that in humans is encoded by the LATS1 gene.[1][2][3]
It has been associated with the Hippo signaling pathway.[4]
The protein encoded by this gene is a putative serine/threonine kinase that localizes to the mitotic apparatus and complexes with cell cycle controller CDC2 kinase in early mitosis. The protein is phosphorylated in a cell-cycle dependent manner, with late prophase phosphorylation remaining through metaphase. The N-terminal region of the protein binds CDC2 to form a complex showing reduced histone H1 kinase activity, indicating a role as a negative regulator of CDC2/cyclin A. In addition, the C-terminal kinase domain binds to its own N-terminal region, suggesting potential negative regulation through interference with complex formation via intramolecular binding. Biochemical and genetic data suggest a role as a tumor suppressor. This is supported by studies in knockout mice showing development of soft-tissue sarcomas, ovarian stromal cell tumors and a high sensitivity to carcinogenic treatments.[3]
Interactions
LATS1 has been shown to interact with Zyxin[5] and Cdk1.[1]
References
- ↑ 1.0 1.1 Tao W, Zhang S, Turenchalk GS, Stewart RA, St John MA, Chen W, Xu T (February 1999). "Human homologue of the Drosophila melanogaster lats tumour suppressor modulates CDC2 activity". Nat Genet. 21 (2): 177–81. doi:10.1038/5960. PMID 9988268.
- ↑ Iida S, Hirota T, Morisaki T, Marumoto T, Hara T, Kuninaka S, Honda S, Kosai K, Kawasuji M, Pallas DC, Saya H (July 2004). "Tumor suppressor WARTS ensures genomic integrity by regulating both mitotic progression and G1 tetraploidy checkpoint function". Oncogene. 23 (31): 5266–74. doi:10.1038/sj.onc.1207623. PMID 15122335.
- ↑ 3.0 3.1 "Entrez Gene: LATS1 LATS, large tumor suppressor, homolog 1 (Drosophila)".
- ↑ Hao Y, Chun A, Cheung K, Rashidi B, Yang X (February 2008). "Tumor suppressor LATS1 is a negative regulator of oncogene YAP". J. Biol. Chem. 283 (9): 5496–509. doi:10.1074/jbc.M709037200. PMID 18158288.
- ↑ Hirota, T; Morisaki T; Nishiyama Y; Marumoto T; Tada K; Hara T; Masuko N; Inagaki M; Hatakeyama K; Saya H (May 2000). "Zyxin, a regulator of actin filament assembly, targets the mitotic apparatus by interacting with h-warts/LATS1 tumor suppressor". J. Cell Biol. UNITED STATES. 149 (5): 1073–86. doi:10.1083/jcb.149.5.1073. ISSN 0021-9525. PMC 2174824. PMID 10831611.
Further reading
- Xu T, Wang W, Zhang S, et al. (1995). "Identifying tumor suppressors in genetic mosaics: the Drosophila lats gene encodes a putative protein kinase". Development. 121 (4): 1053–63. PMID 7743921.
- St John MA, Tao W, Fei X, et al. (1999). "Mice deficient of Lats1 develop soft-tissue sarcomas, ovarian tumours and pituitary dysfunction". Nat. Genet. 21 (2): 182–6. doi:10.1038/5965. PMID 9988269.
- Nishiyama Y, Hirota T, Morisaki T, et al. (1999). "A human homolog of Drosophila warts tumor suppressor, h-warts, localized to mitotic apparatus and specifically phosphorylated during mitosis". FEBS Lett. 459 (2): 159–65. doi:10.1016/S0014-5793(99)01224-7. PMID 10518011.
- Hirota T, Morisaki T, Nishiyama Y, et al. (2000). "Zyxin, a regulator of actin filament assembly, targets the mitotic apparatus by interacting with h-warts/LATS1 tumor suppressor". J. Cell Biol. 149 (5): 1073–86. doi:10.1083/jcb.149.5.1073. PMC 2174824. PMID 10831611.
- Morisaki T, Hirota T, Iida S, et al. (2002). "WARTS tumor suppressor is phosphorylated by Cdc2/cyclin B at spindle poles during mitosis". FEBS Lett. 529 (2–3): 319–24. doi:10.1016/S0014-5793(02)03360-4. PMID 12372621.
- Hisaoka M, Tanaka A, Hashimoto H (2002). "Molecular alterations of h-warts/LATS1 tumor suppressor in human soft tissue sarcoma". Lab. Invest. 82 (10): 1427–35. doi:10.1097/01.lab.0000032381.68634.ca. PMID 12379777.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Kamikubo Y, Takaori-Kondo A, Uchiyama T, Hori T (2003). "Inhibition of cell growth by conditional expression of kpm, a human homologue of Drosophila warts/lats tumor suppressor". J. Biol. Chem. 278 (20): 17609–14. doi:10.1074/jbc.M211974200. PMID 12624101.
- Brill LM, Salomon AR, Ficarro SB, et al. (2004). "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry". Anal. Chem. 76 (10): 2763–72. doi:10.1021/ac035352d. PMID 15144186.
- Yang X, Yu K, Hao Y, et al. (2004). "LATS1 tumour suppressor affects cytokinesis by inhibiting LIMK1". Nat. Cell Biol. 6 (7): 609–17. doi:10.1038/ncb1140. PMID 15220930.
- Beausoleil SA, Jedrychowski M, Schwartz D, et al. (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proc. Natl. Acad. Sci. U.S.A. 101 (33): 12130–5. Bibcode:2004PNAS..10112130B. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Chan EH, Nousiainen M, Chalamalasetty RB, et al. (2005). "The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1". Oncogene. 24 (12): 2076–86. doi:10.1038/sj.onc.1208445. PMID 15688006.
- Takahashi Y, Miyoshi Y, Takahata C, et al. (2005). "Down-regulation of LATS1 and LATS2 mRNA expression by promoter hypermethylation and its association with biologically aggressive phenotype in human breast cancers". Clin. Cancer Res. 11 (4): 1380–5. doi:10.1158/1078-0432.CCR-04-1773. PMID 15746036.
- Kuninaka S, Nomura M, Hirota T, et al. (2005). "The tumor suppressor WARTS activates the Omi / HtrA2-dependent pathway of cell death". Oncogene. 24 (34): 5287–98. doi:10.1038/sj.onc.1208682. PMID 16007220.
- Bothos J, Tuttle RL, Ottey M, et al. (2005). "Human LATS1 is a mitotic exit network kinase". Cancer Res. 65 (15): 6568–75. doi:10.1158/0008-5472.CAN-05-0862. PMID 16061636.
- Jiang Z, Li X, Hu J, et al. (2007). "Promoter hypermethylation-mediated down-regulation of LATS1 and LATS2 in human astrocytoma". Neurosci. Res. 56 (4): 450–8. doi:10.1016/j.neures.2006.09.006. PMID 17049657.
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