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Molecular and Cellular Biology, October 2002, p. 6767-6778, Vol. 22, No. 19
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.19.6767-6778.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Inactivation of the Retinoblastoma Protein Family Can Bypass the HCF-1 Defect in tsBN67 Cell Proliferation and Cytokinesis

Patrick T. Reilly,^1,2, Joanna Wysocka,¹ and Winship Herr^1*

Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724,¹ Program in Molecular and Cellular Biology, State University of New York at Stony Brook, Stony Brook, New York 11794²

Received 14 May 2002/ Returned for modification 6 June 2002/ Accepted 3 July 2002

Owing to a single missense mutation in the cell proliferation factor HCF-1, the temperature-sensitive tsBN67 hamster cell line arrests proliferation at nonpermissive temperatures, primarily in a G₀/G₁ state, and displays temperature-sensitive cytokinesis defects. The HCF-1 mutation in tsBN67 cells also causes a temperature-sensitive dissociation of HCF-1 from chromatin prior to cell proliferation arrest, suggesting that HCF-1-chromatin association is important for mammalian-cell proliferation. Here, we report that the simian virus 40 (SV40) early region, in particular, large T antigen (Tag), and the adenovirus oncoprotein E1A can rescue the tsBN67 cell proliferation defect at nonpermissive temperatures. The SV40 early region rescues the tsBN67 cell proliferation defect without restoring the HCF-1-chromatin association, indicating that these oncoproteins bypass a requirement for HCF-1 function. The SV40 early region also rescues the tsBN67 cytokinesis defect, suggesting that the roles of HCF-1 in cell proliferation and proper cytokinesis are intimately linked. The ability of SV40 Tag and adenovirus E1A to inactivate members of the pRb protein family—pRb, p107, and p130—is important for the bypass of HCF-1 function. These results suggest that HCF-1 regulates mammalian-cell proliferation and cytokinesis, at least in part, by either directly or indirectly opposing pRb family member function.

Present address: Ontario Cancer Institute, Toronto, Ontario, Canada M5G 2C1.

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