TFIIIB is phosphorylated, disrupted and selectively released from tRNA promoters during mitosis in vivo.
Mitosis involves a generalized repression of gene expression. In the case of RNA polymerase III transcription, this is due to phosphorylation-mediated inactivation of TFIIIB, an essential complex comprising the TATA-binding protein TBP and the TAF subunits Brf1 and Bdp1. In HeLa cells, this repression is mediated by a mitotic kinase other than cdc2-cyclin B and is antagonized by protein phosphatase 2A. Brf1 is hyperphosphorylated in metaphase-arrested cells, but remains associated with promoters in condensed chromosomes, along with TBP. In contrast, Bdp1 is selectively released. Repression can be reversed by raising the concentration of Brf1 or Bdp1. The data support a model in which hyperphosphorylation disrupts TFIIIB during mitosis, compromising its ability to support transcription.
Fairley
Jennifer A
JA
Institute of Biomedical and Life Sciences, Division of Biochemistry and Molecular Biology, Davidson Building, University of Glasgow, Glasgow G12 8QQ, UK.
Scott
Pamela H
PH
White
Robert J
RJ
D016203:CDC2 Protein Kinase / Q000378:metabolism; D004258:DNA Polymerase III / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D008938:Mitosis / Q000235:genetics* / Q000502:physiology*; D008954:Models, Biological; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D054648:Protein Phosphatase 2; D012343:RNA, Transfer / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D035381:TATA-Binding Protein Associated Factors / Q000378:metabolism; D035181:TATA-Box Binding Protein / Q000378:metabolism; D035361:Transcription Factor TFIIIB / Q000378:metabolism*
C090956:BRF1 protein, S cerevisiae; C441028:BRF1 protein, human; D029701:Saccharomyces cerevisiae Proteins; D035381:TATA-Binding Protein Associated Factors; D035181:TATA-Box Binding Protein; D035361:Transcription Factor TFIIIB; D012343:RNA, Transfer; D016203:CDC2 Protein Kinase; D004258:DNA Polymerase III; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2