Akt negatively regulates translation of the ternary complex factor Elk-1.
Cross-talk between signaling pathways plays an important role in regulation of cell growth, differentiation, survival, and death. Here, we show that Akt regulates the Elk-1 transcription factor, independent of its negative regulation of Raf kinases. Using a constitutively active Mek1 to bypass the regulation of Raf by Akt, we find that the Elk-1 and Sap1a proteins are dramatically decreased in the presence of activated Akt. Akt catalytic activity is required. Also, Mek-dependent activation of a TCF (Elk-1/Sap-1a)-dependent c-fos reporter is decreased by activated Akt. Neither the level of Elk-1 mRNA nor the stability of the Elk-1 protein is altered by activated Akt. Instead, the rate of incorporation of labeled methionine into Elk-1 protein is decreased in the presence of Akt. In addition, the level of the Elk-1 protein but not GFP is significantly decreased in the presence of activated Akt, when GFP is expressed from an IRES element in a bicistronic message with Elk-1. We conclude that Akt negatively regulates translation of the Elk-1 mRNA. A coding region determinant that maps within the first 279 nts of the Elk-1 message is necessary and sufficient for Akt-mediated regulation of Elk-1.
Figueroa
Claudia
C
Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109-0606, USA.
Vojtek
Anne B
AB
D000818:Animals; D019556:COS Cells; D004268:DNA-Binding Proteins / Q000235:genetics; D017930:Genes, Reporter; D016762:Genes, fos; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D014176:Protein Biosynthesis; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics* / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt; D014157:Transcription Factors; D014158:Transcription, Genetic; D050807:ets-Domain Protein Elk-1; D050808:ets-Domain Protein Elk-4
D004268:DNA-Binding Proteins; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D050808:ets-Domain Protein Elk-4; C494112:ELK1 protein, human; C494193:ELK4 protein, human; C494918:AKT1 protein, human