CK2 forms a stable complex with TFIIIB and activates RNA polymerase III transcription in human cells.
CK2 is a highly conserved protein kinase with growth-promoting and oncogenic properties. It is known to activate RNA polymerase III (PolIII) transcription in Saccharomyces cerevisiae and is shown here to also exert a potent effect on PolIII in mammalian cells. Peptide and chemical inhibitors of CK2 block PolIII transcription in human cell extracts. Furthermore, PolIII transcription in mammalian fibroblasts is decreased significantly when CK2 activity is compromised by chemical inhibitors, antisense oligonucleotides, or kinase-inactive mutants. Coimmunoprecipitation and cofractionation show that endogenous human CK2 associates stably and specifically with the TATA-binding protein-containing factor TFIIIB, which brings PolIII to the initiation site of all class III genes. Serum stimulates TFIIIB phosphorylation in vivo, an effect that is diminished by inhibitors of CK2. Binding to TFIIIC2 recruits TFIIIB to most PolIII promoters; this interaction is compromised specifically by CK2 inhibitors. The data suggest that CK2 stimulates PolIII transcription by binding and phosphorylating TFIIIB and facilitating its recruitment by TFIIIC2. CK2 also activates PolI transcription in mammals and may therefore provide a mechanism to coregulate the output of PolI and PolIII. CK2 provides a rare example of an endogenous activity that operates on the PolIII system in both mammals and yeasts. Such evolutionary conservation suggests that this control may be of fundamental importance.
Johnston
Imogen M
IM
Institute of Biomedical and Life Sciences, Division of Biochemistry and Molecular Biology, University of Glasgow, Glasgow G12 8QQ, United Kingdom.
Allison
Simon J
SJ
Morton
Jennifer P
JP
Schramm
Laura
L
Scott
Pamela H
PH
White
Robert J
RJ
D000818:Animals; D016466:CHO Cells; D047390:Casein Kinase II; D002460:Cell Line; D006224:Cricetinae; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D051379:Mice; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D021122:Protein Subunits; D012320:RNA Polymerase III / Q000235:genetics*; D012343:RNA, Transfer / Q000378:metabolism; D051381:Rats; D035361:Transcription Factor TFIIIB; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects
D004791:Enzyme Inhibitors; D046911:Macromolecular Substances; D021122:Protein Subunits; D035361:Transcription Factor TFIIIB; D014157:Transcription Factors; D012343:RNA, Transfer; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D012320:RNA Polymerase III