Regulation of FoxO activity by CBP/p300-mediated acetylation.
Forkhead box, class O (FoxO) transcription factors are inhibited by insulin-induced FoxO phosphorylation. Recently, acetylation of FoxO factors by calcium response element-binding (CREB)-binding protein (CBP) and/or p300 has been identified as a novel regulatory pathway, although the exact consequences of acetylation remain unclear. We propose that binding of CBP/p300 to FoxO factors is essential for FoxO-mediated transcription. CBP and p300 act as FoxO cofactors by weakening histone-DNA interactions. Acetylation of FoxO factors, however, attenuates FoxO-mediated transcriptional activity by disrupting the interaction between FoxO factors and target DNA. Therefore, acetylation shifts the function of FoxO from cell-cycle arrest and protection against oxidative stress towards cell death.
van der Heide
Lars P
LP
Rudolf Magnus Institute of Neuroscience, UMC Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands.
Smidt
Marten P
MP
D000107:Acetylation; D000818:Animals; D050882:CREB-Binding Protein; D004247:DNA / Q000378:metabolism; D051858:Forkhead Transcription Factors; D006133:Growth Substances / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D011485:Protein Binding; D037761:Sirtuins / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*
D051858:Forkhead Transcription Factors; D006133:Growth Substances; D006657:Histones; D007328:Insulin; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D004247:DNA; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D037761:Sirtuins; D006655:Histone Deacetylases