TY - JOUR
T1 - Human PC4 is a substrate-specific inhibitor of RNA polymerase II phosphorylation
AU - Schang, Luis M.
AU - Hwang, Gwo Jinn H
AU - Dynlacht, Brian D.
AU - Speicher, David W.
AU - Bantly, Andrew
AU - Schaffer, Priscilla A.
AU - Shilatifard, Ali
AU - Ge, Hui
AU - Shiekhattar, Ramin
PY - 2000/3/3
Y1 - 2000/3/3
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.275.9.6071
DO - 10.1074/jbc.275.9.6071
M3 - Article
C2 - 10692395
AN - SCOPUS:0034009073
VL - 275
SP - 6071
EP - 6074
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 9
ER -