CREB binding protein recruitment to the transcription complex requires growth factor-dependent phosphorylation of its GF box.
Growth factors such as epidermal growth factor (EGF) and insulin regulate development and metabolism via genes containing both POU homeodomain (Pit-1) and phorbol ester (AP-1) response elements. Although CREB binding protein (CBP) functions as a coactivator on these elements, the mechanism of transactivation was previously unclear. We now demonstrate that CBP is recruited to these elements only after it is phosphorylated at serine 436 by growth factor-dependent signaling pathways. In contrast, p300, a protein closely related to CBP that lacks this phosphorylation site, binds only weakly to the transcription complex and in a growth factor-independent manner. A small region of CBP (amino acids 312-440), which we term GF box, contains a potent transactivation domain and mediates this effect. Direct phosphorylation represents a novel mechanism controlling coactivator recruitment to the transcription complex.
Zanger
K
K
Division of Pediatric Endocrinology, The University of Chicago, Illinois 60637, USA.
Radovick
S
S
Wondisford
F E
FE
D020816:Amino Acid Motifs; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D050882:CREB-Binding Protein; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D046911:Macromolecular Substances; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011388:Prolactin / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D015534:Trans-Activators / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics; D015533:Transcriptional Activation / Q000187:drug effects*; D014162:Transfection; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D006133:Growth Substances; D046911:Macromolecular Substances; D009687:Nuclear Proteins; C494187:POU1F1 protein, human; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; D011388:Prolactin; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D011493:Protein Kinase C