Regulation of RNA polymerase III transcription during cell cycle entry.
Increased rates of RNA polymerase (pol) III transcription constitute a central feature of the mitogenic response, but little is known about the mechanism(s) responsible. We demonstrate that the retinoblastoma protein RB plays a major role in suppressing pol III transcription in growth-arrested fibroblasts. RB knockout cells are compromised in their ability to down-regulate pol III following serum withdrawal. RB binds and represses the pol III-specific transcription factor TFIIIB during G(0) and early G(1), but this interaction decreases as cells approach S phase. Full induction of pol III coincides with mid- to late G(1) phase, when RB becomes phosphorylated by cyclin D- and E-dependent kinases. TFIIIB only associates with the underphosphorylated form of RB, and overexpression of cyclins D and E stimulates pol III transcription in vivo. The RB-related protein p130 also contributes to the repression of TFIIIB in growth-arrested fibroblasts. These observations provide insight into the mechanisms responsible for controlling pol III transcription during the switch between growth and quiescence.
Scott
P H
PH
Institute of Biomedical and Life Sciences, Division of Biochemistry and Molecular Biology, University of Glasgow, Glasgow G12 8QQ, United Kingdom.
Cairns
C A
CA
Sutcliffe
J E
JE
Alzuherri
H M
HM
McLees
A
A
Winter
A G
AG
White
R J
RJ
D016475:3T3 Cells; D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D016895:Culture Media, Serum-Free; D004247:DNA / Q000096:biosynthesis; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology / Q000502:physiology; D016193:G1 Phase; D016195:G2 Phase; D005786:Gene Expression Regulation; D051379:Mice; D008938:Mitosis; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D012320:RNA Polymerase III / Q000235:genetics / Q000378:metabolism*; D016192:Resting Phase, Cell Cycle; D035361:Transcription Factor TFIIIB; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D016895:Culture Media, Serum-Free; D035361:Transcription Factor TFIIIB; D014157:Transcription Factors; D004247:DNA; D012320:RNA Polymerase III