TY - JOUR
T1 - Akt-mediated YB-1 phosphorylation activates translation of silent mRNA species
AU - Evdokimova, Valentina
AU - Ruzanov, Peter
AU - Anglesio, Michael S.
AU - Sorokin, Alexey V.
AU - Ovchinnikov, Lev P.
AU - Buckley, Jonathan
AU - Triche, Timothy J.
AU - Sonenberg, Nahum
AU - Sorensen, Poul H.B.
PY - 2006/1
Y1 - 2006/1
N2 - 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 non-phosphorylated 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.
AB - 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 non-phosphorylated 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=33645218804&partnerID=8YFLogxK
U2 - 10.1128/MCB.26.1.277-292.2006
DO - 10.1128/MCB.26.1.277-292.2006
M3 - Article
C2 - 16354698
AN - SCOPUS:33645218804
SN - 0270-7306
VL - 26
SP - 277
EP - 292
JO - Molecular and cellular biology
JF - Molecular and cellular biology
IS - 1
ER -