| Structural highlights
Function
[IF6_YEAST] Binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit to form the 80S initiation complex in the cytoplasm. Is also involved in ribosome biogenesis. Associates with pre-60S subunits in the nucleus and is involved in its nuclear export. Cytoplasmic release of TIF6 from 60S subunits and nuclear relocalization is promoted by the GTPase RIA1/EFL1 and by SDO1. Also required for pre-rRNA processing.[1] [2] [3] [4] [5] [6] [PA2G4_HUMAN] May play a role in a ERBB3-regulated signal transduction pathway. Seems be involved in growth regulation. Acts a corepressor of the androgen receptor (AR) and is regulated by the ERBB3 ligand neuregulin-1/heregulin (HRG). Inhibits transcription of some E2F1-regulated promoters, probably by recruiting histone acetylase (HAT) activity. Binds RNA. Associates with 28S, 18S and 5.8S mature rRNAs, several rRNA precursors and probably U3 small nucleolar RNA. May be involved in regulation of intermediate and late steps of rRNA processing. May be involved in ribosome assembly. Mediates cap-independent translation of specific viral IRESs (internal ribosomal entry site) (By similarity).[7] [8] [9] [10]
Publication Abstract from PubMed
Preribosomal particles evolve in the nucleus through transient interaction with biogenesis factors before export to the cytoplasm. Here, we report the architecture of the late pre-60S particle, purified from Saccharomyces cerevisiae, through Arx1, a nuclear export factor with structural homology to methionine aminopeptidases, or its binding partner Alb1. Cryo-EM reconstruction of the Arx1 particle at 11.9-A resolution reveals regions of extra density on the pre-60S particle attributed to associated biogenesis factors, confirming the immature state of the nascent subunit. One of these densities could be unambiguously assigned to Arx1. Immunoelectron microscopy and UV cross-linking localize Arx1 close to the ribosomal exit tunnel, in direct contact with ES27, a highly dynamic eukaryotic rRNA expansion segment. The binding of Arx1 at the exit tunnel may position this export factor to prevent premature recruitment of ribosome-associated factors active during translation.
Structure of the pre-60S ribosomal subunit with nuclear export factor Arx1 bound at the exit tunnel.,Bradatsch B, Leidig C, Granneman S, Gnadig M, Tollervey D, Bottcher B, Beckmann R, Hurt E Nat Struct Mol Biol. 2012 Nov 11. doi: 10.1038/nsmb.2438. PMID:23142978[11]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sanvito F, Piatti S, Villa A, Bossi M, Lucchini G, Marchisio PC, Biffo S. The beta4 integrin interactor p27(BBP/eIF6) is an essential nuclear matrix protein involved in 60S ribosomal subunit assembly. J Cell Biol. 1999 Mar 8;144(5):823-37. PMID:10085284
- ↑ Senger B, Lafontaine DL, Graindorge JS, Gadal O, Camasses A, Sanni A, Garnier JM, Breitenbach M, Hurt E, Fasiolo F. The nucle(ol)ar Tif6p and Efl1p are required for a late cytoplasmic step of ribosome synthesis. Mol Cell. 2001 Dec;8(6):1363-73. PMID:11779510
- ↑ Basu U, Si K, Warner JR, Maitra U. The Saccharomyces cerevisiae TIF6 gene encoding translation initiation factor 6 is required for 60S ribosomal subunit biogenesis. Mol Cell Biol. 2001 Mar;21(5):1453-62. PMID:11238882 doi:10.1128/MCB.21.5.1453-1462.2001
- ↑ Menne TF, Goyenechea B, Sanchez-Puig N, Wong CC, Tonkin LM, Ancliff PJ, Brost RL, Costanzo M, Boone C, Warren AJ. The Shwachman-Bodian-Diamond syndrome protein mediates translational activation of ribosomes in yeast. Nat Genet. 2007 Apr;39(4):486-95. Epub 2007 Mar 11. PMID:17353896 doi:ng1994
- ↑ Ray P, Basu U, Ray A, Majumdar R, Deng H, Maitra U. The Saccharomyces cerevisiae 60 S ribosome biogenesis factor Tif6p is regulated by Hrr25p-mediated phosphorylation. J Biol Chem. 2008 Apr 11;283(15):9681-91. doi: 10.1074/jbc.M710294200. Epub 2008 , Feb 5. PMID:18256024 doi:10.1074/jbc.M710294200
- ↑ Groft CM, Beckmann R, Sali A, Burley SK. Crystal structures of ribosome anti-association factor IF6. Nat Struct Biol. 2000 Dec;7(12):1156-64. PMID:11101899 doi:10.1038/82017
- ↑ Xia X, Cheng A, Lessor T, Zhang Y, Hamburger AW. Ebp1, an ErbB-3 binding protein, interacts with Rb and affects Rb transcriptional regulation. J Cell Physiol. 2001 May;187(2):209-17. PMID:11268000 doi:http://dx.doi.org/10.1002/jcp.1075
- ↑ Zhang Y, Woodford N, Xia X, Hamburger AW. Repression of E2F1-mediated transcription by the ErbB3 binding protein Ebp1 involves histone deacetylases. Nucleic Acids Res. 2003 Apr 15;31(8):2168-77. PMID:12682367
- ↑ Squatrito M, Mancino M, Donzelli M, Areces LB, Draetta GF. EBP1 is a nucleolar growth-regulating protein that is part of pre-ribosomal ribonucleoprotein complexes. Oncogene. 2004 May 27;23(25):4454-65. PMID:15064750 doi:http://dx.doi.org/10.1038/sj.onc.1207579
- ↑ Zhang Y, Hamburger AW. Specificity and heregulin regulation of Ebp1 (ErbB3 binding protein 1) mediated repression of androgen receptor signalling. Br J Cancer. 2005 Jan 17;92(1):140-6. PMID:15583694 doi:http://dx.doi.org/6602257
- ↑ Bradatsch B, Leidig C, Granneman S, Gnadig M, Tollervey D, Bottcher B, Beckmann R, Hurt E. Structure of the pre-60S ribosomal subunit with nuclear export factor Arx1 bound at the exit tunnel. Nat Struct Mol Biol. 2012 Nov 11. doi: 10.1038/nsmb.2438. PMID:23142978 doi:http://dx.doi.org/10.1038/nsmb.2438
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