Human PC4 is a substrate-specific inhibitor of RNA polymerase II phosphorylation

Luis M. Schang, Gwo Jinn H. Hwang, Brian D. Dynlacht, David W. Speicher, Andrew Bantly, Priscilla A. Schaffer, Ali Shilatifard, Hui Ge, Ramin Shiekhattar

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

The activity of cyclin-dependent protein kinases (cdks) is physiologically regulated by phosphorylation, association with the specific cyclin subunits, and repression by specific cdk inhibitors. All three physiological regulatory mechanisms are specific for one or more cdks, but none is known to be substrate specific. In contrast, synthetic cdk peptide inhibitors that specifically inhibit cdk phosphorylation of only some substrates, 'aptamers,' have been described. Here, we show that PC4, a naturally occurring transcriptional coactivator, competitively inhibits cdk- 1, -2, and -7-mediated phosphorylation of the largest subunit of RNA polymerase II (RNAPII), but it does not inhibit phosphorylation of other substrates of the same kinases. Interestingly, the phosphorylated form of PC4 is devoid of kinase inhibitory activity. We also show that wild-type PC4 but not the kinase inhibitory-deficient mutant of PC4 represses transcription in vivo. Our results point to a novel role for PC4 as a specific inhibitor of RNAPII phosphorylation.

Original languageEnglish (US)
Pages (from-to)6071-6074
Number of pages4
JournalJournal of Biological Chemistry
Volume275
Issue number9
DOIs
StatePublished - Mar 3 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Schang, L. M., Hwang, G. J. H., Dynlacht, B. D., Speicher, D. W., Bantly, A., Schaffer, P. A., Shilatifard, A., Ge, H., & Shiekhattar, R. (2000). Human PC4 is a substrate-specific inhibitor of RNA polymerase II phosphorylation. Journal of Biological Chemistry, 275(9), 6071-6074. https://doi.org/10.1074/jbc.275.9.6071