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Cyclin D1 expression is regulated by the retinoblastoma protein

Item Type:Article
Title:Cyclin D1 expression is regulated by the retinoblastoma protein
Creators Name:Mueller, H. and Lukas, J. and Schneider, A. and Warthoe, P. and Bartek, J. and Eilers, M. and Strauss, M.
Abstract:The product of the retinoblastoma susceptibility gene, pRb, acts as a tumor suppressor and loss of its function is involved in the development of various types of cancer. DNA tumor viruses are supposed to disturb the normal regulation of the cell cycle by inactivating pRb. However, a direct function of pRb in regulation of the cell cycle has hitherto not been shown. We demonstrate here that the cell cycle-dependent expression of one of the G1-phase cyclins, cyclin D1, is dependent on the presence of a functional Rb protein. Rb-deficient tumor cell lines as well as cells expressing viral oncoproteins (large tumor antigen of simian virus 40, early region 1A of adenovirus, early region 7 of papillomavirus) have low or barely detectable levels of cyclin D1. Expression of cyclin D1, but not of cyclins A and E, is induced by transfection of the Rb gene into Rb-deficient tumor cells. Cotransfection of a reporter gene under the control of the D1 promoter, together with the Rb gene, into Rb-deficient cell lines demonstrates stimulation of the D1 promoter by Rb, which parallels the stimulation of endogenous cyclin D1 gene expression. Our finding that pRb stimulates expression of a key component of cell cycle control, cyclin D1, suggests the existence of a regulatory loop between pRb and cyclin D1 and extends existing models of tumor suppressor function.
Keywords:Base Sequence, Cell Cycle, Cyclin D1, Cyclins, DNA Primers, Gene Expression Regulation, Molecular Sequence Data, Oncogene Proteins, Genetic Promoter Regions, Messenger RNA, Retinoblastoma Protein, Cultured Tumor Cells
Source:Proceedings of the National Academy of Sciences of the United States of America
ISSN:0027-8424
Publisher:National Academy of Sciences (U.S.A.)
Volume:91
Number:8
Page Range:2945-2949
Date:12 April 1994
Official Publication:http://www.pnas.org/content/91/8/2945.abstract
PubMed:View item in PubMed

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