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Gradual phosphorylation regulates PC4 coactivator function.
Jonker, Hendrik R A; Wechselberger, Rainer W; Pinkse, Martijn; Kaptein, Robert; Folkers, Gert E.
Afiliação
  • Jonker HR; Department of NMR Spectroscopy, Bijvoet Center for Biomolecular Research, Utrecht University, the Netherlands.
FEBS J ; 273(7): 1430-44, 2006 Apr.
Article em En | MEDLINE | ID: mdl-16689930
ABSTRACT
The unstructured N-terminal domain of the transcriptional cofactor PC4 contains multiple phosphorylation sites that regulate activity. The phosphorylation status differentially influences the various biochemical functions performed by the structured core of PC4. Binding to ssDNA is slightly enhanced by phosphorylation of one serine residue, which is not augmented by further phosphorylation. The presence of at least two phosphoserines decreases DNA-unwinding activity and abrogates binding to the transcriptional activator VP16. Phosphorylation gradually decreases the binding affinity for dsDNA. These phosphorylation-dependent changes in PC4 activities correlate with the sequential functions PC4 fulfils throughout the transcription cycle. MS and NMR revealed that up to eight serines are progressively phosphorylated towards the N-terminus, resulting in gradual environmental changes in the C-terminal direction of the following lysine-rich region. Also within the structured core, primarily around the interaction surfaces, environmental changes are observed. We propose a model for co-ordinated changes in PC4 cofactor functions, mediated by phosphorylation status-dependent gradual masking of the lysine-rich region causing shielding or exposure of interaction surfaces.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / Proteínas de Ligação a DNA Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2006 Tipo de documento: Article
Buscar no Google
Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / Proteínas de Ligação a DNA Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2006 Tipo de documento: Article