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Molecular and Cellular Biology, September 2001, p. 5806-5814, Vol. 21, No. 17
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.17.5806-5814.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Overlapping Functions of the pRb Family in the Regulation of rRNA Synthesis

Sonia Ciarmatori,1 Pamela H. Scott,2 Josephine E. Sutcliffe,2 Angela McLees,2 Hadi M. Alzuherri,2 Jan-Hermen Dannenberg,3 Hein te Riele,3 Ingrid Grummt,1 Renate Voit,1,* and Robert J. White2

Division of Molecular Biology of the Cell II, German Cancer Research Centre, D-69120 Heidelberg, Germany1; Institute of Biomedical and Life Sciences, Division of Biochemistry and Molecular Biology, University of Glasgow, Glasgow G12 8QQ, United Kingdom2; and The Netherlands Cancer Institute, Division of Molecular Biology, 1066 CX Amsterdam, The Netherlands3

Received 5 February 2001/Returned for modification 9 March 2001/Accepted 7 May 2001

The "pocket" proteins pRb, p107, and p130 are a family of negative growth regulators. Previous studies have demonstrated that overexpression of pRb can repress transcription by RNA polymerase (Pol) I. To assess whether pRb performs this role under physiological conditions, we have examined pre-rRNA levels in cells from mice lacking either pRb alone or combinations of the three pocket proteins. Pol I transcription was unaffected in pRb-knockout fibroblasts, but specific disruption of the entire pRb family deregulated rRNA synthesis. Further analysis showed that p130 shares with pRb the ability to repress Pol I transcription, whereas p107 is ineffective in this system. Production of rRNA is abnormally elevated in Rb-/- p130-/- fibroblasts. Furthermore, overexpression of p130 can inhibit an rRNA promoter both in vitro and in vivo. This reflects an ability of p130 to bind and inactivate the upstream binding factor, UBF. The data imply that rRNA synthesis in living cells is subject to redundant control by endogenous pRb and p130.

* Corresponding author. Mailing address: Division of Molecular Biology of the Cell II, German Cancer Research Centre, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. Phone: 49-6221-423-441. Fax: 49-6221-423-404. E-mail: r.voit{at}dkfz-heidelberg.de.

Molecular and Cellular Biology, September 2001, p. 5806-5814, Vol. 21, No. 17
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.17.5806-5814.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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