Akt-mediated YB-1 phosphorylation activates translation of silent mRNA species.
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.
Evdokimova
Valentina
V
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
P
Anglesio
Michael S
MS
Sorokin
Alexey V
AV
Ovchinnikov
Lev P
LP
Buckley
Jonathan
J
Triche
Timothy J
TJ
Sonenberg
Nahum
N
Sorensen
Poul H B
PH
D000818:Animals; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D014176:Protein Biosynthesis / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D039381:RNA Cap-Binding Proteins / Q000378:metabolism*; D012315:RNA Caps / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism; D051840:Y-Box-Binding Protein 1 / Q000378:metabolism*
D039381:RNA Cap-Binding Proteins; D012315:RNA Caps; D012333:RNA, Messenger; D012261:Ribonucleoproteins; D051840:Y-Box-Binding Protein 1; C026452:messenger ribonucleoprotein; D051057:Proto-Oncogene Proteins c-akt