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[[Hemidesmosome]]s are structures which link the [[basal lamina]] to the intermediate filament [[cytoskeleton]]. An important functional component of hemidesmosomes is the integrin beta-4 subunit ([[ITGB4]]), a protein containing two fibronectin type III domains. The protein encoded by this gene binds to the fibronectin type III domains of ITGB4 and may help link ITGB4 to the intermediate filament cytoskeleton. The encoded protein, which is insoluble and found both in the [[Cell nucleus|nucleus]] and in the [[cytoplasm]], can function as a [[eukaryotic initiation factor|translation initiation factor]] and catalyzes the association of the [[40S]] and [[60S]] [[ribosome|ribosomal]] subunits along with eIF5 bound to GTP. Multiple transcript variants encoding several different [[protein isoform|isoforms]] have been found for this gene.<ref name="entrez">{{cite web | title = Entrez Gene: ITGB4BP integrin beta 4 binding protein| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3692| accessdate = }}</ref>
[[Hemidesmosome]]s are structures which link the [[basal lamina]] to the intermediate filament [[cytoskeleton]]. An important functional component of hemidesmosomes is the integrin beta-4 subunit ([[ITGB4]]), a protein containing two fibronectin type III domains. The protein encoded by this gene binds to the fibronectin type III domains of ITGB4 and may help link ITGB4 to the intermediate filament cytoskeleton. The encoded protein, which is insoluble and found both in the [[Cell nucleus|nucleus]] and in the [[cytoplasm]], can function as a [[eukaryotic initiation factor|translation initiation factor]] and catalyzes the association of the [[40S]] and [[60S]] [[ribosome|ribosomal]] subunits along with eIF5 bound to GTP. Multiple transcript variants encoding several different [[protein isoform|isoforms]] have been found for this gene.<ref name="entrez">{{cite web | title = Entrez Gene: ITGB4BP integrin beta 4 binding protein| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3692| accessdate = }}</ref>


==Interactions==
== Overview ==
EIF6 has been shown to [[Protein-protein interaction|interact]] with [[FHL2]],<ref name=pmid10906324>{{cite journal |last=Wixler |first=V |author2=Geerts D |author3=Laplantine E |author4=Westhoff D |author5=Smyth N |author6=Aumailley M |author7=Sonnenberg A |author8=Paulsson M  |date=October 2000  |title=The LIM-only protein DRAL/FHL2 binds to the cytoplasmic domain of several alpha and beta integrin chains and is recruited to adhesion complexes |journal=J. Biol. Chem. |volume=275 |issue=43 |pages=33669–78 |publisher= |location = UNITED STATES| issn = 0021-9258| pmid = 10906324 |doi = 10.1074/jbc.M002519200 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = }}</ref> [[ITGB4]]<ref name=pmid9374518>{{cite journal |last=Biffo |first=S |author2=Sanvito F |author3=Costa S |author4=Preve L |author5=Pignatelli R |author6=Spinardi L |author7=Marchisio P C  |date=November 1997  |title=Isolation of a novel beta4 integrin-binding protein (p27(BBP)) highly expressed in epithelial cells |journal=J. Biol. Chem. |volume=272 |issue=48 |pages=30314–21 |publisher= |location = UNITED STATES| issn = 0021-9258| pmid = 9374518 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = |doi=10.1074/jbc.272.48.30314 }}</ref> and [[GNB2L1]].<ref name=pmid14654845>{{cite journal |last=Ceci |first=Marcello |author2=Gaviraghi Cristina |author3=Gorrini Chiara |author4=Sala Leonardo A |author5=Offenhäuser Nina |author6=Marchisio Pier Carlo |author7=Biffo Stefano  |date=December 2003  |title=Release of eIF6 (p27BBP) from the 60S subunit allows 80S ribosome assembly |journal=[[Nature (journal)|Nature]] |volume=426 |issue=6966 |pages=579–84 |publisher= |location = England| issn = | pmid = 14654845 |doi = 10.1038/nature02160 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = }}</ref>
EIF6 plays important roles in 80S ribosome formation, cell growth and gene expression. eukaryotic ribosome is 80S ribosome, which can separate to 40S and 60S subunits. EIF6 helps to product mature 60s subunit and then EIF6 should disassociate with 60s subunit so that it can binds to 40s subunit to form ribosome. Keeping in balance of EIF6 is essential for the body: few EIF6 helps synthesis of normal ribosome, while large amount of EIF6 inhibited 60s subunits bind to 40s subunits.<ref>{{cite journal | vauthors = Brina D, Grosso S, Miluzio A, Biffo S | title = Translational control by 80S formation and 60S availability: the central role of eIF6, a rate limiting factor in cell cycle progression and tumorigenesis | journal = Cell Cycle | volume = 10 | issue = 20 | pages = 3441–6 | date = October 2011 | pmid = 22031223 | doi = 10.4161/cc.10.20.17796 }}</ref>


==References==
 
== Function ==
EIF6 exists both in nucleolus and cytoplasm. In the eukaryotic nucleolus, a 90S pre-ribosomal complex separate to a 60S pre-ribosomal complex and a 40S pre-ribosomal complex, which are involved in synthesis of mature ribosome. EIF6 is indispensable in 60S subunit biogenesis and deletion of EIF6 has lethal effect. The partial deletion of eIF6 results in decreasing of free 60S ribosomal subunit, which means it knocks the 40S/60S subunit ratio off balance,and limiting the speed of protein synthesis. 60S pre-ribosomal complex associated with eIF6 shuttle from nucleolus to cytoplasm and then eIF6 disassociated with pre-60S so that 60S subunit can binds to 40S subunit and continues to subsequent prograss. EIF6 can act as a rate-limiting translational initiation factor, and its expression levels influence the translational rate. Few of eIF6 will small accelerate protein translation, while large of eIF6 will block translational process by inhibiting production of ribosome.<ref>{{cite journal | vauthors = Brina D, Miluzio A, Ricciardi S, Biffo S | title = eIF6 anti-association activity is required for ribosome biogenesis, translational control and tumor progression | journal = Biochimica et Biophysica Acta | volume = 1849 | issue = 7 | pages = 830–5 | date = July 2015 | pmid = 25252159 | doi = 10.1016/j.bbagrm.2014.09.010 }}</ref> The activity of eIF6 also cause glycolysis and fatty acid synthesis by mRNAs' translational controlling.<ref>{{cite journal | vauthors = Biffo S, Manfrini N, Ricciardi S | title = Crosstalks between translation and metabolism in cancer | journal = Current Opinion in Genetics & Development | volume = 48 | pages = 75–81 | date = February 2018 | pmid = 29153483 | doi = 10.1016/j.gde.2017.10.011 }}</ref>
 
== Expression ==
EIF6 has different level of expression in different tissue and cell. EIF6 has high level of expression in stem cells and cycling cells, while it doesn't in postmitotic cells; high level in brain and epithelia, while low level in muscle.<ref>{{cite journal | vauthors = Miluzio A, Beugnet A, Volta V, Biffo S | title = Eukaryotic initiation factor 6 mediates a continuum between 60S ribosome biogenesis and translation | journal = EMBO Reports | volume = 10 | issue = 5 | pages = 459–65 | date = May 2009 | pmid = 19373251 | doi = 10.1038/embor.2009.70 }}</ref>
 
== Interactions ==
 
EIF6 has been shown to [[Protein-protein interaction|interact]] with [[FHL2]],<ref name=pmid10906324>{{cite journal | vauthors = Wixler V, Geerts D, Laplantine E, Westhoff D, Smyth N, Aumailley M, Sonnenberg A, Paulsson M | title = The LIM-only protein DRAL/FHL2 binds to the cytoplasmic domain of several alpha and beta integrin chains and is recruited to adhesion complexes | journal = The Journal of Biological Chemistry | volume = 275 | issue = 43 | pages = 33669–78 | date = October 2000 | pmid = 10906324 | doi = 10.1074/jbc.M002519200 }}</ref> [[ITGB4]]<ref name=pmid9374518>{{cite journal | vauthors = Biffo S, Sanvito F, Costa S, Preve L, Pignatelli R, Spinardi L, Marchisio PC | title = Isolation of a novel beta4 integrin-binding protein (p27(BBP)) highly expressed in epithelial cells | journal = The Journal of Biological Chemistry | volume = 272 | issue = 48 | pages = 30314–21 | date = November 1997 | pmid = 9374518 | doi = 10.1074/jbc.272.48.30314 }}</ref> and [[GNB2L1]].<ref name=pmid14654845>{{cite journal | vauthors = Ceci M, Gaviraghi C, Gorrini C, Sala LA, Offenhäuser N, Marchisio PC, Biffo S | title = Release of eIF6 (p27BBP) from the 60S subunit allows 80S ribosome assembly | journal = Nature | volume = 426 | issue = 6966 | pages = 579–84 | date = December 2003 | pmid = 14654845 | doi = 10.1038/nature02160 }}</ref>
 
EIF6 plays important roles in 80S ribosome formation, cell growth and gene expression.<ref>{{cite journal | vauthors = Brina D, Grosso S, Miluzio A, Biffo S | title = Translational control by 80S formation and 60S availability: the central role of eIF6, a rate limiting factor in cell cycle progression and tumorigenesis | journal = Cell Cycle | volume = 10 | issue = 20 | pages = 3441–6 | date = October 2011 | pmid = 22031223 | doi = 10.4161/cc.10.20.17796 }}</ref>
 
== See also ==
*[[Eukaryotic initiation factor]]
*[[Eukaryotic large ribosomal subunit (60S)]]
 
== References ==
{{reflist}}
{{reflist}}


==Further reading==
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = Biffo S, Sanvito F, Costa S, Preve L, Pignatelli R, Spinardi L, Marchisio PC | title = Isolation of a novel beta4 integrin-binding protein (p27(BBP)) highly expressed in epithelial cells | journal = The Journal of Biological Chemistry | volume = 272 | issue = 48 | pages = 30314–21 | date = November 1997 | pmid = 9374518 | doi = 10.1074/jbc.272.48.30314 }}
| citations =
* {{cite journal | vauthors = Si K, Chaudhuri J, Chevesich J, Maitra U | title = Molecular cloning and functional expression of a human cDNA encoding translation initiation factor 6 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 26 | pages = 14285–90 | date = December 1997 | pmid = 9405604 | pmc = 24943 | doi = 10.1073/pnas.94.26.14285 }}
*{{cite journal | vauthors=Biffo S, Sanvito F, Costa S |title=Isolation of a novel beta4 integrin-binding protein (p27(BBP)) highly expressed in epithelial cells |journal=J. Biol. Chem. |volume=272 |issue= 48 |pages= 30314–21 |year= 1997 |pmid= 9374518 |doi=10.1074/jbc.272.48.30314 |display-authors=etal}}
* {{cite journal | vauthors = Mao M, Fu G, Wu JS, Zhang QH, Zhou J, Kan LX, Huang QH, He KL, Gu BW, Han ZG, Shen Y, Gu J, Yu YP, Xu SH, Wang YX, Chen SJ, Chen Z | title = Identification of genes expressed in human CD34(+) hematopoietic stem/progenitor cells by expressed sequence tags and efficient full-length cDNA cloning | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 95 | issue = 14 | pages = 8175–80 | date = July 1998 | pmid = 9653160 | pmc = 20949 | doi = 10.1073/pnas.95.14.8175 }}
*{{cite journal | vauthors=Si K, Chaudhuri J, Chevesich J, Maitra U |title=Molecular cloning and functional expression of a human cDNA encoding translation initiation factor 6 |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=94 |issue= 26 |pages= 14285–90 |year= 1998 |pmid= 9405604 |doi=10.1073/pnas.94.26.14285 | pmc=24943  }}
* {{cite journal | vauthors = Sanvito F, Arrigo G, Zuffardi O, Agnelli M, Marchisio PC, Biffo S | title = Localization of p27 beta4 binding protein gene (ITGB4BP) to human chromosome region 20q11.2 | journal = Genomics | volume = 52 | issue = 1 | pages = 111–2 | date = August 1998 | pmid = 9740680 | doi = 10.1006/geno.1998.5403 }}
*{{cite journal | vauthors=Mao M, Fu G, Wu JS |title=Identification of genes expressed in human CD34+ hematopoietic stem/progenitor cells by expressed sequence tags and efficient full-length cDNA cloning |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=95 |issue= 14 |pages= 8175–80 |year= 1998 |pmid= 9653160 |doi=10.1073/pnas.95.14.8175 | pmc=20949  |display-authors=etal}}
* {{cite journal | vauthors = Sanvito F, Piatti S, Villa A, Bossi M, Lucchini G, Marchisio PC, Biffo S | title = The beta4 integrin interactor p27(BBP/eIF6) is an essential nuclear matrix protein involved in 60S ribosomal subunit assembly | journal = The Journal of Cell Biology | volume = 144 | issue = 5 | pages = 823–37 | date = March 1999 | pmid = 10085284 | pmc = 2148184 | doi = 10.1083/jcb.144.5.823 }}
*{{cite journal | vauthors=Sanvito F, Arrigo G, Zuffardi O |title=Localization of p27 beta4 binding protein gene (ITGB4BP) to human chromosome region 20q11.2 |journal= Genomics|volume=52 |issue= 1 |pages= 111–2 |year= 1998|pmid= 9740680 |doi= 10.1006/geno.1998.5403 |display-authors=etal}}
* {{cite journal | vauthors = Wixler V, Geerts D, Laplantine E, Westhoff D, Smyth N, Aumailley M, Sonnenberg A, Paulsson M | title = The LIM-only protein DRAL/FHL2 binds to the cytoplasmic domain of several alpha and beta integrin chains and is recruited to adhesion complexes | journal = The Journal of Biological Chemistry | volume = 275 | issue = 43 | pages = 33669–78 | date = October 2000 | pmid = 10906324 | doi = 10.1074/jbc.M002519200 }}
*{{cite journal | vauthors=Sanvito F, Piatti S, Villa A |title=The β4 Integrin Interactor p27BBP/eIF6 Is an Essential Nuclear Matrix Protein Involved in 60S Ribosomal Subunit Assembly |journal=J. Cell Biol. |volume=144 |issue= 5 |pages= 823–37 |year= 1999 |pmid= 10085284 |doi=10.1083/jcb.144.5.823 | pmc=2148184  |display-authors=etal}}
* {{cite journal | vauthors = Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, Fu G, Shen Y, Fan HY, Lu G, Zhong M, Xu XR, Han ZG, Zhang JW, Tao J, Huang QH, Zhou J, Hu GX, Gu J, Chen SJ, Chen Z | title = Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells | journal = Genome Research | volume = 10 | issue = 10 | pages = 1546–60 | date = October 2000 | pmid = 11042152 | pmc = 310934 | doi = 10.1101/gr.140200 }}
*{{cite journal | vauthors=Wixler V, Geerts D, Laplantine E |title=The LIM-only protein DRAL/FHL2 binds to the cytoplasmic domain of several alpha and beta integrin chains and is recruited to adhesion complexes |journal=J. Biol. Chem. |volume=275 |issue= 43 |pages= 33669–78 |year= 2000 |pmid= 10906324 |doi= 10.1074/jbc.M002519200 |display-authors=etal}}
* {{cite journal | vauthors = Donadini A, Giodini A, Sanvito F, Marchisio PC, Biffo S | title = The human ITGB4BP gene is constitutively expressed in vitro, but highly modulated in vivo | journal = Gene | volume = 266 | issue = 1–2 | pages = 35–43 | date = March 2001 | pmid = 11290417 | doi = 10.1016/S0378-1119(01)00370-5 }}
*{{cite journal | vauthors=Zhang QH, Ye M, Wu XY |title=Cloning and Functional Analysis of cDNAs with Open Reading Frames for 300 Previously Undefined Genes Expressed in CD34+ Hematopoietic Stem/Progenitor Cells |journal=Genome Res. |volume=10 |issue= 10 |pages= 1546–60 |year= 2001 |pmid= 11042152 |doi=10.1101/gr.140200 | pmc=310934  |display-authors=etal}}
* {{cite journal | vauthors = Andersen JS, Lyon CE, Fox AH, Leung AK, Lam YW, Steen H, Mann M, Lamond AI | title = Directed proteomic analysis of the human nucleolus | journal = Current Biology | volume = 12 | issue = 1 | pages = 1–11 | date = January 2002 | pmid = 11790298 | doi = 10.1016/S0960-9822(01)00650-9 }}
*{{cite journal | vauthors=Donadini A, Giodini A, Sanvito F |title=The human ITGB4BP gene is constitutively expressed in vitro, but highly modulated in vivo |journal=Gene |volume=266 |issue= 1–2 |pages= 35–43 |year= 2001 |pmid= 11290417 |doi=10.1016/S0378-1119(01)00370-5 |display-authors=etal}}
* {{cite journal | vauthors = Basu U, Si K, Deng H, Maitra U | title = Phosphorylation of mammalian eukaryotic translation initiation factor 6 and its Saccharomyces cerevisiae homologue Tif6p: evidence that phosphorylation of Tif6p regulates its nucleocytoplasmic distribution and is required for yeast cell growth | journal = Molecular and Cellular Biology | volume = 23 | issue = 17 | pages = 6187–99 | date = September 2003 | pmid = 12917340 | pmc = 180954 | doi = 10.1128/MCB.23.17.6187-6199.2003 }}
*{{cite journal | vauthors=Deloukas P, Matthews LH, Ashurst J |title=The DNA sequence and comparative analysis of human chromosome 20 |journal=Nature |volume=414 |issue= 6866 |pages= 865–71 |year= 2002 |pmid= 11780052 |doi= 10.1038/414865a |display-authors=etal}}
* {{cite journal | vauthors = Ceci M, Gaviraghi C, Gorrini C, Sala LA, Offenhäuser N, Marchisio PC, Biffo S | title = Release of eIF6 (p27BBP) from the 60S subunit allows 80S ribosome assembly | journal = Nature | volume = 426 | issue = 6966 | pages = 579–84 | date = December 2003 | pmid = 14654845 | doi = 10.1038/nature02160 }}
*{{cite journal  | vauthors=Andersen JS, Lyon CE, Fox AH |title=Directed proteomic analysis of the human nucleolus |journal=Curr. Biol. |volume=12 |issue= 1 |pages= 1–11 |year= 2002 |pmid= 11790298 |doi=10.1016/S0960-9822(01)00650-9 |display-authors=etal}}
* {{cite journal | vauthors = Rosso P, Cortesina G, Sanvito F, Donadini A, Di Benedetto B, Biffo S, Marchisio PC | title = Overexpression of p27BBP in head and neck carcinomas and their lymph node metastases | journal = Head & Neck | volume = 26 | issue = 5 | pages = 408–17 | date = May 2004 | pmid = 15122657 | doi = 10.1002/hed.10401 }}
*{{cite journal  | vauthors=Strausberg RL, Feingold EA, Grouse LH |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 |display-authors=etal}}
* {{cite journal | vauthors = Lehner B, Sanderson CM | title = A protein interaction framework for human mRNA degradation | journal = Genome Research | volume = 14 | issue = 7 | pages = 1315–23 | date = July 2004 | pmid = 15231747 | pmc = 442147 | doi = 10.1101/gr.2122004 }}
*{{cite journal | vauthors=Basu U, Si K, Deng H, Maitra U |title=Phosphorylation of Mammalian Eukaryotic Translation Initiation Factor 6 and Its Saccharomyces cerevisiae Homologue Tif6p: Evidence that Phosphorylation of Tif6p Regulates Its Nucleocytoplasmic Distribution and Is Required for Yeast Cell Growth |journal=Mol. Cell. Biol. |volume=23 |issue= 17 |pages= 6187–99 |year= 2003 |pmid= 12917340 |doi=10.1128/MCB.23.17.6187-6199.2003 | pmc=180954  }}
* {{cite journal | vauthors = Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ | title = Immunoaffinity profiling of tyrosine phosphorylation in cancer cells | journal = Nature Biotechnology | volume = 23 | issue = 1 | pages = 94–101 | date = January 2005 | pmid = 15592455 | doi = 10.1038/nbt1046 }}
*{{cite journal | vauthors=Ceci M, Gaviraghi C, Gorrini C |title=Release of eIF6 (p27BBP) from the 60S subunit allows 80S ribosome assembly |journal=Nature |volume=426 |issue= 6966 |pages= 579–84 |year= 2003 |pmid= 14654845 |doi= 10.1038/nature02160 |display-authors=etal}}
* {{cite journal | vauthors = Andersen JS, Lam YW, Leung AK, Ong SE, Lyon CE, Lamond AI, Mann M | title = Nucleolar proteome dynamics | journal = Nature | volume = 433 | issue = 7021 | pages = 77–83 | date = January 2005 | pmid = 15635413 | doi = 10.1038/nature03207 }}
*{{cite journal | vauthors=Rosso P, Cortesina G, Sanvito F |title=Overexpression of p27BBP in head and neck carcinomas and their lymph node metastases |journal=Head Neck |volume=26 |issue= 5 |pages= 408–17 |year= 2004 |pmid= 15122657 |doi= 10.1002/hed.10401 |display-authors=etal}}
* {{cite journal | vauthors = Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toksöz E, Droege A, Krobitsch S, Korn B, Birchmeier W, Lehrach H, Wanker EE | title = A human protein-protein interaction network: a resource for annotating the proteome | journal = Cell | volume = 122 | issue = 6 | pages = 957–68 | date = September 2005 | pmid = 16169070 | doi = 10.1016/j.cell.2005.08.029 }}
*{{cite journal | vauthors=Lehner B, Sanderson CM |title=A Protein Interaction Framework for Human mRNA Degradation |journal=Genome Res. |volume=14 |issue= 7 |pages= 1315–23 |year= 2004 |pmid= 15231747 |doi= 10.1101/gr.2122004  | pmc=442147 }}
*{{cite journal  | vauthors=Gerhard DS, Wagner L, Feingold EA |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 |display-authors=etal}}
*{{cite journal | vauthors=Rush J, Moritz A, Lee KA |title=Immunoaffinity profiling of tyrosine phosphorylation in cancer cells |journal=Nat. Biotechnol. |volume=23 |issue= 1 |pages= 94–101 |year= 2005 |pmid= 15592455 |doi= 10.1038/nbt1046 |display-authors=etal}}
*{{cite journal | vauthors=Andersen JS, Lam YW, Leung AK |title=Nucleolar proteome dynamics |journal=Nature |volume=433 |issue= 7021 |pages= 77–83 |year= 2005 |pmid= 15635413 |doi= 10.1038/nature03207 |display-authors=etal}}
*{{cite journal | vauthors=Stelzl U, Worm U, Lalowski M |title=A human protein-protein interaction network: a resource for annotating the proteome |journal=Cell |volume=122 |issue= 6 |pages= 957–68 |year= 2005 |pmid= 16169070 |doi= 10.1016/j.cell.2005.08.029 |display-authors=etal}}
}}
{{refend}}
{{refend}}


{{Initiation factors}}
{{Initiation factors}}


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Latest revision as of 07:15, 10 January 2019

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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View/Edit Human

Eukaryotic translation initiation factor 6 (EIF6), also known as Integrin beta 4 binding protein (ITGB4BP), is a human gene.[1]

Hemidesmosomes are structures which link the basal lamina to the intermediate filament cytoskeleton. An important functional component of hemidesmosomes is the integrin beta-4 subunit (ITGB4), a protein containing two fibronectin type III domains. The protein encoded by this gene binds to the fibronectin type III domains of ITGB4 and may help link ITGB4 to the intermediate filament cytoskeleton. The encoded protein, which is insoluble and found both in the nucleus and in the cytoplasm, can function as a translation initiation factor and catalyzes the association of the 40S and 60S ribosomal subunits along with eIF5 bound to GTP. Multiple transcript variants encoding several different isoforms have been found for this gene.[1]

Overview

EIF6 plays important roles in 80S ribosome formation, cell growth and gene expression. eukaryotic ribosome is 80S ribosome, which can separate to 40S and 60S subunits. EIF6 helps to product mature 60s subunit and then EIF6 should disassociate with 60s subunit so that it can binds to 40s subunit to form ribosome. Keeping in balance of EIF6 is essential for the body: few EIF6 helps synthesis of normal ribosome, while large amount of EIF6 inhibited 60s subunits bind to 40s subunits.[2]


Function

EIF6 exists both in nucleolus and cytoplasm. In the eukaryotic nucleolus, a 90S pre-ribosomal complex separate to a 60S pre-ribosomal complex and a 40S pre-ribosomal complex, which are involved in synthesis of mature ribosome. EIF6 is indispensable in 60S subunit biogenesis and deletion of EIF6 has lethal effect. The partial deletion of eIF6 results in decreasing of free 60S ribosomal subunit, which means it knocks the 40S/60S subunit ratio off balance,and limiting the speed of protein synthesis. 60S pre-ribosomal complex associated with eIF6 shuttle from nucleolus to cytoplasm and then eIF6 disassociated with pre-60S so that 60S subunit can binds to 40S subunit and continues to subsequent prograss. EIF6 can act as a rate-limiting translational initiation factor, and its expression levels influence the translational rate. Few of eIF6 will small accelerate protein translation, while large of eIF6 will block translational process by inhibiting production of ribosome.[3] The activity of eIF6 also cause glycolysis and fatty acid synthesis by mRNAs' translational controlling.[4]

Expression

EIF6 has different level of expression in different tissue and cell. EIF6 has high level of expression in stem cells and cycling cells, while it doesn't in postmitotic cells; high level in brain and epithelia, while low level in muscle.[5]

Interactions

EIF6 has been shown to interact with FHL2,[6] ITGB4[7] and GNB2L1.[8]

EIF6 plays important roles in 80S ribosome formation, cell growth and gene expression.[9]

See also

References

  1. ↑ 1.0 1.1 "Entrez Gene: ITGB4BP integrin beta 4 binding protein".
  2. ↑ Brina D, Grosso S, Miluzio A, Biffo S (October 2011). "Translational control by 80S formation and 60S availability: the central role of eIF6, a rate limiting factor in cell cycle progression and tumorigenesis". Cell Cycle. 10 (20): 3441–6. doi:10.4161/cc.10.20.17796. PMID 22031223.
  3. ↑ Brina D, Miluzio A, Ricciardi S, Biffo S (July 2015). "eIF6 anti-association activity is required for ribosome biogenesis, translational control and tumor progression". Biochimica et Biophysica Acta. 1849 (7): 830–5. doi:10.1016/j.bbagrm.2014.09.010. PMID 25252159.
  4. ↑ Biffo S, Manfrini N, Ricciardi S (February 2018). "Crosstalks between translation and metabolism in cancer". Current Opinion in Genetics & Development. 48: 75–81. doi:10.1016/j.gde.2017.10.011. PMID 29153483.
  5. ↑ Miluzio A, Beugnet A, Volta V, Biffo S (May 2009). "Eukaryotic initiation factor 6 mediates a continuum between 60S ribosome biogenesis and translation". EMBO Reports. 10 (5): 459–65. doi:10.1038/embor.2009.70. PMID 19373251.
  6. ↑ Wixler V, Geerts D, Laplantine E, Westhoff D, Smyth N, Aumailley M, Sonnenberg A, Paulsson M (October 2000). "The LIM-only protein DRAL/FHL2 binds to the cytoplasmic domain of several alpha and beta integrin chains and is recruited to adhesion complexes". The Journal of Biological Chemistry. 275 (43): 33669–78. doi:10.1074/jbc.M002519200. PMID 10906324.
  7. ↑ Biffo S, Sanvito F, Costa S, Preve L, Pignatelli R, Spinardi L, Marchisio PC (November 1997). "Isolation of a novel beta4 integrin-binding protein (p27(BBP)) highly expressed in epithelial cells". The Journal of Biological Chemistry. 272 (48): 30314–21. doi:10.1074/jbc.272.48.30314. PMID 9374518.
  8. ↑ Ceci M, Gaviraghi C, Gorrini C, Sala LA, Offenhäuser N, Marchisio PC, Biffo S (December 2003). "Release of eIF6 (p27BBP) from the 60S subunit allows 80S ribosome assembly". Nature. 426 (6966): 579–84. doi:10.1038/nature02160. PMID 14654845.
  9. ↑ Brina D, Grosso S, Miluzio A, Biffo S (October 2011). "Translational control by 80S formation and 60S availability: the central role of eIF6, a rate limiting factor in cell cycle progression and tumorigenesis". Cell Cycle. 10 (20): 3441–6. doi:10.4161/cc.10.20.17796. PMID 22031223.

Further reading


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