CK2 forms a stable complex with TFIIIB and activates RNA polymerase III transcription in human cells

Imogen M. Johnston, Simon J. Allison, Jennifer P. Morton, Laura Schramm, Pamela H. Scott, Robert J. White

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

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.

LanguageEnglish
Pages3757-3768
Number of pages12
JournalMolecular and Cellular Biology
Volume22
Issue number11
DOIs
Publication statusPublished - 2002
Externally publishedYes

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Transcription Factor TFIIIB
RNA Polymerase III
Mammals
TATA-Box Binding Protein
Antisense Oligonucleotides
Cell Extracts
Protein Kinases
Saccharomyces cerevisiae
Phosphotransferases
Fibroblasts
Yeasts
Phosphorylation
Peptides
Growth
Serum
Genes

Cite this

Johnston, Imogen M. ; Allison, Simon J. ; Morton, Jennifer P. ; Schramm, Laura ; Scott, Pamela H. ; White, Robert J. / CK2 forms a stable complex with TFIIIB and activates RNA polymerase III transcription in human cells. In: Molecular and Cellular Biology. 2002 ; Vol. 22, No. 11. pp. 3757-3768.
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CK2 forms a stable complex with TFIIIB and activates RNA polymerase III transcription in human cells. / Johnston, Imogen M.; Allison, Simon J.; Morton, Jennifer P.; Schramm, Laura; Scott, Pamela H.; White, Robert J.

In: Molecular and Cellular Biology, Vol. 22, No. 11, 2002, p. 3757-3768.

Research output: Contribution to journalArticle

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