Home LiteratureArticle Details
PMID: 16354698 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Akt-mediated YB-1 phosphorylation activates translation of silent mRNA species.

Molecular and cellular biology ·Vol. 26 ·No. 1 ·2006-01-00 ·Pages 277-92

Evdokimova V, Ruzanov P, Anglesio MS, Sorokin AV, Ovchinnikov LP, Buckley J, Triche TJ, Sonenberg N, Sorensen PH

Abstract

YB-1 is a broad-specificity RNA-binding protein that is involved in regulation of mRNA transcription, splicing, translation, and stability. In both germinal and somatic cells, YB-1 and related proteins are major components of translationally inactive messenger ribonucleoprotein particles (mRNPs) and are mainly responsible for storage of mRNAs in a silent state. However, mechanisms regulating the repressor activity of YB-1 are not well understood. Here we demonstrate that association of YB-1 with the capped 5' terminus of the mRNA is regulated via phosphorylation by the serine/threonine protein kinase Akt. In contrast to its nonphosphorylated form, phosphorylated YB-1 fails to inhibit cap-dependent but not internal ribosome entry site-dependent translation of a reporter mRNA in vitro. We also show that similar to YB-1, Akt is associated with inactive mRNPs and that activated Akt may relieve translational repression of the YB-1-bound mRNAs. Using Affymetrix microarrays, we found that many of the YB-1-associated messages encode stress- and growth-related proteins, raising the intriguing possibility that Akt-mediated YB-1 phosphorylation could, in part, increase production of proteins regulating cell proliferation, oncogenic transformation, and stress response.

MeSH Terms
Animals Gene Expression Regulation Gene Silencing Humans Mice NIH 3T3 Cells Oligonucleotide Array Sequence Analysis Phosphorylation Protein Biosynthesis/genetics Proto-Oncogene Proteins c-akt/metabolism RNA Cap-Binding Proteins/metabolism RNA Caps/metabolism RNA, Messenger/metabolism Ribonucleoproteins/metabolism Y-Box-Binding Protein 1/metabolism
Chemicals
RNA Cap-Binding Proteins RNA Caps RNA, Messenger Ribonucleoproteins Y-Box-Binding Protein 1 messenger ribonucleoprotein Proto-Oncogene Proteins c-akt
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Evdokimova Valentina
Department of Pathology, British Columbia Research Institute for Children's and Women's Health, Vancouver, BC, Canada V5Z 163. evdokimo@interchange.ubc.ca
Ruzanov Peter
Anglesio Michael S
Sorokin Alexey V
Ovchinnikov Lev P
Buckley Jonathan
Triche Timothy J
Sonenberg Nahum
Sorensen Poul H B
References (45)
45 references, click to expand
  1. The pleiotropic functions of the Y-box-binding protein, YB-1.
    Bioessays. 2003 Jul;25(7):691-8 PMID: 12815724
  2. Structural and functional properties of the evolutionarily ancient Y-box family of nucleic acid binding proteins.
    Bioessays. 1994 Apr;16(4):245-51 PMID: 8031301
  3. Y box-binding protein 1 induces resistance to oncogenic transformation by the phosphatidylinositol 3-kinase pathway.
    Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12384-9 PMID: 14530393
  4. Oncogenic Ras and Akt signaling contribute to glioblastoma formation by differential recruitment of existing mRNAs to polysomes.
    Mol Cell. 2003 Oct;12(4):889-901 PMID: 14580340
  5. A multi-protein complex containing cold shock domain (Y-box) and polypyrimidine tract binding proteins forms on the vascular endothelial growth factor mRNA. Potential role in mRNA stabilization.
    Eur J Biochem. 2004 Feb;271(3):648-60 PMID: 14728692
  6. The major protein of messenger ribonucleoprotein particles in somatic cells is a member of the Y-box binding transcription factor family.
    J Biol Chem. 1995 Feb 17;270(7):3186-92 PMID: 7852402
  7. Masking of mRNA by Y-box proteins.
    FASEB J. 1996 Mar;10(4):435-43 PMID: 8647342
  8. Matrix adhesion and Ras transformation both activate a phosphoinositide 3-OH kinase and protein kinase B/Akt cellular survival pathway.
    EMBO J. 1997 May 15;16(10):2783-93 PMID: 9184223
  9. Overexpression in COS cells of p50, the major core protein associated with mRNA, results in translation inhibition.
    Nucleic Acids Res. 1997 Jul 15;25(14):2911-6 PMID: 9207042
  10. The mammalian target of rapamycin phosphorylates sites having a (Ser/Thr)-Pro motif and is activated by antibodies to a region near its COOH terminus.
    J Biol Chem. 1997 Dec 19;272(51):32547-50 PMID: 9405468
  11. The mRNA 5' cap-binding protein eIF4E and control of cell growth.
    Curr Opin Cell Biol. 1998 Apr;10(2):268-75 PMID: 9561852
  12. Gene regulation by Y-box proteins: coupling control of transcription and translation.
    Trends Cell Biol. 1998 Aug;8(8):318-23 PMID: 9704408
  13. Translational regulation by Y-box transcription factor: involvement of the major mRNA-associated protein, p50.
    Int J Biochem Cell Biol. 1999 Jan;31(1):139-49 PMID: 10216949
  14. Regulation of 4E-BP1 phosphorylation: a novel two-step mechanism.
    Genes Dev. 1999 Jun 1;13(11):1422-37 PMID: 10364159
  15. An acidic protein, YBAP1, mediates the release of YB-1 from mRNA and relieves the translational repression activity of YB-1.
    Mol Cell Biol. 2005 Mar;25(5):1779-92 PMID: 15713634
  16. Inhibition of protein synthesis by Y box-binding protein 1 blocks oncogenic cell transformation.
    Mol Cell Biol. 2005 Mar;25(6):2095-106 PMID: 15743808
  17. Akt phosphorylates the Y-box binding protein 1 at Ser102 located in the cold shock domain and affects the anchorage-independent growth of breast cancer cells.
    Oncogene. 2005 Jun 16;24(26):4281-92 PMID: 15806160
  18. Proteasome-mediated cleavage of the Y-box-binding protein 1 is linked to DNA-damage stress response.
    EMBO J. 2005 Oct 19;24(20):3602-12 PMID: 16193061
  19. RNA-binding proteins TIA-1 and TIAR link the phosphorylation of eIF-2 alpha to the assembly of mammalian stress granules.
    J Cell Biol. 1999 Dec 27;147(7):1431-42 PMID: 10613902
  20. Akt/protein kinase B is regulated by autophosphorylation at the hypothetical PDK-2 site.
    J Biol Chem. 2000 Mar 24;275(12):8271-4 PMID: 10722653
  21. 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
  22. eIF4 initiation factors: effectors of mRNA recruitment to ribosomes and regulators of translation.
    Annu Rev Biochem. 1999;68:913-63 PMID: 10872469
  23. Identifying mRNA subsets in messenger ribonucleoprotein complexes by using cDNA arrays.
    Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14085-90 PMID: 11121017
  24. Thrombin induces the release of the Y-box protein dbpB from mRNA: a mechanism of transcriptional activation.
    Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7277-82 PMID: 11390977
  25. The major mRNA-associated protein YB-1 is a potent 5' cap-dependent mRNA stabilizer.
    EMBO J. 2001 Oct 1;20(19):5491-502 PMID: 11574481
  26. 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
  27. The major messenger ribonucleoprotein particle protein p50 (YB-1) promotes nucleic acid strand annealing.
    J Biol Chem. 2001 Nov 30;276(48):44841-7 PMID: 11585833
  28. The mRNA-binding protein YB-1 (p50) prevents association of the eukaryotic initiation factor eIF4G with mRNA and inhibits protein synthesis at the initiation stage.
    J Biol Chem. 2003 Apr 18;278(16):13936-43 PMID: 12582179
  29. An essential role for protein synthesis in oncogenic cellular transformation.
    Oncogene. 2004 Apr 19;23(18):3145-50 PMID: 15094764
  30. Postgenomic global analysis of translational control induced by oncogenic signaling.
    Oncogene. 2004 Apr 19;23(18):3248-64 PMID: 15094774
  31. Sensitivity and specificity of five abundance estimators for high-density oligonucleotide microarrays.
    Bioinformatics. 2004 May 1;20(7):1060-5 PMID: 14764574
  32. Regulation of translation and cancer.
    Cell Cycle. 2004 Apr;3(4):452-5 PMID: 14976427
  33. Upstream and downstream of mTOR.
    Genes Dev. 2004 Aug 15;18(16):1926-45 PMID: 15314020
  34. Structural organization of mRNA complexes with major core mRNP protein YB-1.
    Nucleic Acids Res. 2004;32(18):5621-35 PMID: 15494450
  35. A protein of molecular weight 78,000 bound to the polyadenylate region of eukaryotic messenger RNAs.
    Proc Natl Acad Sci U S A. 1973 Mar;70(3):924-8 PMID: 4515002
  36. Identification in Xenopus laevis of a class of oocyte-specific proteins bound to messenger RNA.
    Eur J Biochem. 1981 Jan;113(3):415-24 PMID: 7215334
  37. Reversible inhibition of translation by Xenopus oocyte-specific proteins.
    Nature. 1984 May 24-30;309(5966):378-80 PMID: 6727992
  38. Characterization of the cDNA encoding a protein binding to the major histocompatibility complex class II Y box.
    Proc Natl Acad Sci U S A. 1988 Oct;85(19):7322-6 PMID: 3174636
  39. Translational active mRNPs from rabbit reticulocytes are qualitatively different from free mRNA in their translatability in cell-free system.
    FEBS Lett. 1989 Nov 6;257(2):257-9 PMID: 2583271
  40. Xenopus Y-box transcription factors: molecular cloning, functional analysis and developmental regulation.
    Proc Natl Acad Sci U S A. 1990 Nov;87(22):9028-32 PMID: 2247479
  41. An analysis of vertebrate mRNA sequences: intimations of translational control.
    J Cell Biol. 1991 Nov;115(4):887-903 PMID: 1955461
  42. A regulatory cis element and a specific binding factor involved in the mitogenic control of murine ribosomal protein L32 translation.
    J Biol Chem. 1992 Jan 5;267(1):508-14 PMID: 1309750
  43. Role of cytoplasmic mRNP proteins in translation.
    Biochimie. 1992 May;74(5):477-83 PMID: 1637873
  44. Masking mRNA from translation in somatic cells.
    Genes Dev. 1993 Sep;7(9):1725-36 PMID: 8370522
  45. YB-1 as a cell cycle-regulated transcription factor facilitating cyclin A and cyclin B1 gene expression.
    J Biol Chem. 2003 Jul 25;278(30):27988-96 PMID: 12695516
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.26.1.277-292.2006
Email
evdokimo@interchange.ubc.ca
Published
2006-01-00
Pages
277-92
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC1317623
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.26.1.277-292.2006 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2