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EIF6

Summary

Eukaryotic translation initiation factor 6 (EIF6), also known as Integrin beta 4 binding protein (ITGB4BP), is a human gene.[5]

EIF6
Identifiers
AliasesEIF6, CAB, EIF3A, ITGB4BP, b(2)gcn, eIF-6, p27(BBP), p27BBP, eukaryotic translation initiation factor 6
External IDsOMIM: 602912 MGI: 1196288 HomoloGene: 7135 GeneCards: EIF6
Orthologs
SpeciesHumanMouse
Entrez

3692

16418

Ensembl

ENSG00000242372

ENSMUSG00000027613

UniProt

P56537

O55135

RefSeq (mRNA)

NM_010579

RefSeq (protein)

NP_001254739
NP_002203
NP_852131
NP_852133

NP_034709

Location (UCSC)Chr 20: 35.28 – 35.28 MbChr 2: 155.66 – 155.67 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[5]

EIF6 plays important roles in Eukaryotic 80S ribosome formation, cell growth and gene expression. The 80S ribosome, which can separate into 40S and 60S subunits. EIF6 helps to protect 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.[6]

Function edit

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 progress. 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.[7] The activity of eIF6 also cause glycolysis and fatty acid synthesis by mRNAs' translational controlling.[8]

Structure edit

 
An x-ray crystallography-based model of eIF6 structure from S. cerevisiae

eIF6 is 245 amino acids long.

Expression edit

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.[9]

Interactions edit

EIF6 has been shown to interact with FHL2,[10] ITGB4[11] and GNB2L1.[12]

EIF6 plays important roles in 80S ribosome formation, cell growth and gene expression.[13]

Evolution edit

eIF6 is present in both yeast and humans, and its amino acid sequence is 77% identical between the two.[7] No duplications of eIF6, or even conserved motifs within the protein are known.[7]

History edit

eIF6 activity was first described by work in the early 1980s from Linda L. Spremulli's and Umadas Maitra's laboratories.[7] The gene was eventually cloned by Maitra's and Gene Carlo Marchisio's groups, both publishing their work in 1997.[7]

See also edit

References edit

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000242372 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027613 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b "Entrez Gene: ITGB4BP integrin beta 4 binding protein".
  6. ^ 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.
  7. ^ a b c d e 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 (BBA) - Gene Regulatory Mechanisms. 1849 (7): 830–5. doi:10.1016/j.bbagrm.2014.09.010. PMID 25252159.
  8. ^ 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.
  9. ^ 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. PMC 2680881. PMID 19373251.
  10. ^ 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.
  11. ^ 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.
  12. ^ 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. Bibcode:2003Natur.426..579C. doi:10.1038/nature02160. PMID 14654845. S2CID 2431706.
  13. ^ 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 edit

  • 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.
  • Si K, Chaudhuri J, Chevesich J, Maitra U (December 1997). "Molecular cloning and functional expression of a human cDNA encoding translation initiation factor 6". Proceedings of the National Academy of Sciences of the United States of America. 94 (26): 14285–90. Bibcode:1997PNAS...9414285S. doi:10.1073/pnas.94.26.14285. PMC 24943. PMID 9405604.
  • 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 (July 1998). "Identification of genes expressed in human CD34(+) hematopoietic stem/progenitor cells by expressed sequence tags and efficient full-length cDNA cloning". Proceedings of the National Academy of Sciences of the United States of America. 95 (14): 8175–80. Bibcode:1998PNAS...95.8175M. doi:10.1073/pnas.95.14.8175. PMC 20949. PMID 9653160.
  • Sanvito F, Arrigo G, Zuffardi O, Agnelli M, Marchisio PC, Biffo S (August 1998). "Localization of p27 beta4 binding protein gene (ITGB4BP) to human chromosome region 20q11.2". Genomics. 52 (1): 111–2. doi:10.1006/geno.1998.5403. PMID 9740680.
  • Sanvito F, Piatti S, Villa A, Bossi M, Lucchini G, Marchisio PC, Biffo S (March 1999). "The beta4 integrin interactor p27(BBP/eIF6) is an essential nuclear matrix protein involved in 60S ribosomal subunit assembly". The Journal of Cell Biology. 144 (5): 823–37. doi:10.1083/jcb.144.5.823. PMC 2148184. PMID 10085284.
  • 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.
  • 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 (October 2000). "Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells". Genome Research. 10 (10): 1546–60. doi:10.1101/gr.140200. PMC 310934. PMID 11042152.
  • Donadini A, Giodini A, Sanvito F, Marchisio PC, Biffo S (March 2001). "The human ITGB4BP gene is constitutively expressed in vitro, but highly modulated in vivo". Gene. 266 (1–2): 35–43. doi:10.1016/S0378-1119(01)00370-5. PMID 11290417.
  • Andersen JS, Lyon CE, Fox AH, Leung AK, Lam YW, Steen H, Mann M, Lamond AI (January 2002). "Directed proteomic analysis of the human nucleolus". Current Biology. 12 (1): 1–11. Bibcode:2002CBio...12....1A. doi:10.1016/S0960-9822(01)00650-9. PMID 11790298. S2CID 14132033.
  • Basu U, Si K, Deng H, Maitra U (September 2003). "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". Molecular and Cellular Biology. 23 (17): 6187–99. doi:10.1128/MCB.23.17.6187-6199.2003. PMC 180954. PMID 12917340.
  • 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. Bibcode:2003Natur.426..579C. doi:10.1038/nature02160. PMID 14654845. S2CID 2431706.
  • Rosso P, Cortesina G, Sanvito F, Donadini A, Di Benedetto B, Biffo S, Marchisio PC (May 2004). "Overexpression of p27BBP in head and neck carcinomas and their lymph node metastases". Head & Neck. 26 (5): 408–17. CiteSeerX 10.1.1.503.9652. doi:10.1002/hed.10401. PMID 15122657. S2CID 39531947.
  • Lehner B, Sanderson CM (July 2004). "A protein interaction framework for human mRNA degradation". Genome Research. 14 (7): 1315–23. doi:10.1101/gr.2122004. PMC 442147. PMID 15231747.
  • Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ (January 2005). "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells". Nature Biotechnology. 23 (1): 94–101. doi:10.1038/nbt1046. PMID 15592455. S2CID 7200157.
  • Andersen JS, Lam YW, Leung AK, Ong SE, Lyon CE, Lamond AI, Mann M (January 2005). "Nucleolar proteome dynamics". Nature. 433 (7021): 77–83. Bibcode:2005Natur.433...77A. doi:10.1038/nature03207. PMID 15635413. S2CID 4344740.
  • 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 (September 2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell. 122 (6): 957–68. doi:10.1016/j.cell.2005.08.029. hdl:11858/00-001M-0000-0010-8592-0. PMID 16169070. S2CID 8235923.