Akt phosphorylation of La regulates specific mRNA translation in glial progenitors.
The Akt signaling pathway activity increases as normal tissue progresses to malignant transformation, and regulates the translation of specific messenger RNAs (mRNAs) through multiple mechanisms. We have identified one such mechanism of Akt-dependent translation control as involving the lupus autoantigen La. La is an RNA-associated protein that contains multiple trafficking elements to support the interaction with RNAs in different subcellular locations. We show here that the La protein is a direct target of the serine/threonine protein kinase Akt on threonine 301, and La nuclear export in mouse glial progenitors, as well as its association with polysomes is modulated by Akt activity. Using a functional approach to determine the network of genes affected by La in the cytoplasm by microarray analysis of polysome-bound mRNAs, we found that La binds 34% of the polysome bound mRNAs and regulates the expression of a specific pool of mRNAs under KRas/Akt activation. Therefore, La appears to be an important contributor to Akt-mediated translational regulation of these transcripts in murine glial cells.
Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. fab2008@med.cornell.edu
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Brenet
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Socci
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Sonenberg
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Holland
D021581:Active Transport, Cell Nucleus; D000818:Animals; D001324:Autoantigens / Q000378:metabolism*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D051379:Mice; D009457:Neuroglia / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D015689:Oncogene Protein p21(ras) / Q000378:metabolism; D010766:Phosphorylation; D011132:Polyribosomes / Q000378:metabolism; D014176:Protein Biosynthesis / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012261:Ribonucleoproteins / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism*; D014158:Transcription, Genetic; D000097585:SS-B Antigen
D001324:Autoantigens; D015689:Oncogene Protein p21(ras); D051057:Proto-Oncogene Proteins c-akt; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D012261:Ribonucleoproteins; D000097585:SS-B Antigen