Phosphorylation negatively regulates the function of coactivator PC4.
Human positive cofactor 4 (PC4) mediates activator-dependent transcription by RNA polymerase II, apparently through interactions with transcriptional activators and the basal transcription machinery. We report here that PC4 function is modulated by in vivo phosphorylation. Protein-protein interaction studies and in vitro transcription assays demonstrate that only the nonphosphorylated form of PC4 is functionally active. Although recombinant PC4 can be phosphorylated by casein kinase II and protein kinase C in vitro, mutational and mass spectrometric analyses suggest that the in vivo hyperphosphorylation of PC4 is mediated mainly by casein kinase II and restricted to an N-terminal serine-rich region. These observations provide one example of a transcriptional cofactor that is negatively regulated by casein kinase II phosphorylation.
Ge
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Laboratory of Biochemistry and Molecular Biology, Rockefeller University, New York, NY 10021.
Zhao
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Y
Chait
B T
BT
Roeder
R G
RG
D000595:Amino Acid Sequence; D047390:Casein Kinase II; D005786:Gene Expression Regulation; D006367:HeLa Cells; D017405:Herpes Simplex Virus Protein Vmw65 / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins; D066298:In Vitro Techniques; D013058:Mass Spectrometry; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D010449:Peptide Mapping; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012097:Repressor Proteins; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D017405:Herpes Simplex Virus Protein Vmw65; C490043:IFRD2 protein, human; D017874:Immediate-Early Proteins; D008565:Membrane Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D010768:Phosphoserine; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C