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Originally published In Press as doi:10.1074/jbc.M005417200 on October 9, 2000

J. Biol. Chem., Vol. 276, Issue 2, 1005-1014, January 12, 2001
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Regulation of RNA Polymerase III Transcription during Cell Cycle Entry*

Pamela H. ScottDagger , Carol A. Cairns, Josephine E. Sutcliffe, Hadi M. Alzuherri, Angela McLees, Andrew G. Winter, and Robert J. White§

From the Institute of Biomedical and Life Sciences, Division of Biochemistry and Molecular Biology, University of Glasgow, Glasgow G12 8QQ, United Kingdom

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 G0 and early G1, but this interaction decreases as cells approach S phase. Full induction of pol III coincides with mid- to late G1 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.

* This work was supported in part by Research Career Development Fellowship 055409 (to P. H. S.) from the Wellcome Trust, by Biotechnology and Biological Sciences Research Council Grant CO5766 (to R. J. W.), and by Association for International Cancer Research Grant 98-46 (to R. J. W.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger A Wellcome Trust Research Fellow.

§ A Jenner Research Fellow of the Lister Institute of Preventive Medicine. To whom correspondence should be addressed. Tel.: 44-141-330-4628; Fax: 44-141-330-4620; E-mail: rwhite@udcf.gla.ac.uk.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.


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