title: Recruitment of p300 by C/EBPbeta triggers phosphorylation of p300 and modulates coactivator activity.
abstract: Transcriptional coactivators such as p300 act as crucial elements in the eukaryotic gene regulation network. These proteins bind to various transcription factors which recruit them to specific gene regions whose chromatin structure subsequently is remodeled. Previously, we have shown that C/EBPbeta recruits p300 by interacting with the E1A-binding site of the coactivator. We now show that C/EBPbeta not only binds to p300 but also triggers massive phosphorylation of p300. This novel activity of C/EBPbeta is dependent on the E1A-binding region of p300 as well as on several subdomains of C/EBPbeta, all of which are involved in the p300-C/EBPbeta interaction. We have identified several sites of C/EBPbeta-inducible phosphorylation within the C-terminal domain of p300. Mutation of these sites substantially impairs the activity of p300 as a coactivator of C/EBPbeta. Interestingly, phosphorylation of p300 is also triggered by other C/EBP family members as well as by various other transcription factors that interact with the E1A-binding domain of p300, suggesting that this novel phosphorylation mechanism may be of general relevance.
authors.affiliation: Institut für Biochemie, Westfälische-Wilhelms-Universität Münster, Wilhelm-Klemm-Strasse 2, D-48149 Münster, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Schwartz
authors.forename: Kristina
authors.initials: K
authors.lastname: Beck
authors.forename: Sigrun
authors.initials: S
authors.lastname: Mink
authors.forename: Mirco
authors.initials: M
authors.lastname: Schmolke
authors.forename: Bastian
authors.initials: B
authors.lastname: Budde
authors.forename: Dorit
authors.initials: D
authors.lastname: Wenning
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Klempnauer
mesh_terms: D002454:Cell Differentiation / Q000502:physiology; D002467:Cell Nucleus; D022423:Myeloid Cells / Q000502:physiology; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors