6a6l

Structural highlights

Function

YBOX1_HUMAN Mediates pre-mRNA alternative splicing regulation. Binds to splice sites in pre-mRNA and regulates splice site selection. Binds and stabilizes cytoplasmic mRNA. Contributes to the regulation of translation by modulating the interaction between the mRNA and eukaryotic initiation factors (By similarity). Regulates the transcription of numerous genes. Its transcriptional activity on the multidrug resistance gene MDR1 is enhanced in presence of the APEX1 acetylated form at 'Lys-6' and 'Lys-7'. Binds to promoters that contain a Y-box (5'-CTGATTGGCCAA-3'), such as MDR1 and HLA class II genes. Promotes separation of DNA strands that contain mismatches or are modified by cisplatin. Has endonucleolytic activity and can introduce nicks or breaks into double-stranded DNA (in vitro). May play a role in DNA repair. Component of the CRD-mediated complex that promotes MYC mRNA stability. Binds preferentially to the 5'-[CU]CUGCG-3' motif in vitro.^{[1] [2] [3] [4] [5] [6] [7] [8]} The secreted form acts as an extracellular mitogen and stimulates cell migration and proliferation.

References

1. ↑ Chen CY, Gherzi R, Andersen JS, Gaietta G, Jurchott K, Royer HD, Mann M, Karin M. Nucleolin and YB-1 are required for JNK-mediated interleukin-2 mRNA stabilization during T-cell activation. Genes Dev. 2000 May 15;14(10):1236-48. PMID:10817758
2. ↑ Capowski EE, Esnault S, Bhattacharya S, Malter JS. Y box-binding factor promotes eosinophil survival by stabilizing granulocyte-macrophage colony-stimulating factor mRNA. J Immunol. 2001 Nov 15;167(10):5970-6. PMID:11698476
3. ↑ Raffetseder U, Frye B, Rauen T, Jurchott K, Royer HD, Jansen PL, Mertens PR. Splicing factor SRp30c interaction with Y-box protein-1 confers nuclear YB-1 shuttling and alternative splice site selection. J Biol Chem. 2003 May 16;278(20):18241-8. doi: 10.1074/jbc.M212518200. Epub 2003 , Feb 25. PMID:12604611 doi:http://dx.doi.org/10.1074/jbc.M212518200
4. ↑ Gaudreault I, Guay D, Lebel M. YB-1 promotes strand separation in vitro of duplex DNA containing either mispaired bases or cisplatin modifications, exhibits endonucleolytic activities and binds several DNA repair proteins. Nucleic Acids Res. 2004 Jan 12;32(1):316-27. doi: 10.1093/nar/gkh170. Print 2004. PMID:14718551 doi:http://dx.doi.org/10.1093/nar/gkh170
5. ↑ Onishi H, Kino Y, Morita T, Futai E, Sasagawa N, Ishiura S. MBNL1 associates with YB-1 in cytoplasmic stress granules. J Neurosci Res. 2008 Jul;86(9):1994-2002. doi: 10.1002/jnr.21655. PMID:18335541 doi:10.1002/jnr.21655
6. ↑ Chattopadhyay R, Das S, Maiti AK, Boldogh I, Xie J, Hazra TK, Kohno K, Mitra S, Bhakat KK. Regulatory role of human AP-endonuclease (APE1/Ref-1) in YB-1-mediated activation of the multidrug resistance gene MDR1. Mol Cell Biol. 2008 Dec;28(23):7066-80. doi: 10.1128/MCB.00244-08. Epub 2008 Sep , 22. PMID:18809583 doi:10.1128/MCB.00244-08
7. ↑ Weidensdorfer D, Stohr N, Baude A, Lederer M, Kohn M, Schierhorn A, Buchmeier S, Wahle E, Huttelmaier S. Control of c-myc mRNA stability by IGF2BP1-associated cytoplasmic RNPs. RNA. 2009 Jan;15(1):104-15. doi: 10.1261/rna.1175909. Epub 2008 Nov 24. PMID:19029303 doi:10.1261/rna.1175909
8. ↑ Frye BC, Halfter S, Djudjaj S, Muehlenberg P, Weber S, Raffetseder U, En-Nia A, Knott H, Baron JM, Dooley S, Bernhagen J, Mertens PR. Y-box protein-1 is actively secreted through a non-classical pathway and acts as an extracellular mitogen. EMBO Rep. 2009 Jul;10(7):783-9. doi: 10.1038/embor.2009.81. Epub 2009 May 29. PMID:19483673 doi:http://dx.doi.org/10.1038/embor.2009.81