title: Inactivation of the retinoblastoma protein family can bypass the HCF-1 defect in tsBN67 cell proliferation and cytokinesis.
abstract: 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 G(0)/G(1) 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.
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Reilly
authors.forename: Joanna
authors.initials: J
authors.lastname: Wysocka
authors.forename: Winship
authors.initials: W
authors.lastname: Herr
mesh_terms: D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D020816:Amino Acid Motifs / Q000502:physiology; D000818:Animals; D000957:Antigens, Viral, Tumor / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D006224:Cricetinae; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D051863:Host Cell Factor C1; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D050717:Retinoblastoma-Like Protein p130; D016196:S Phase / Q000187:drug effects / Q000502:physiology; D013539:Simian virus 40 / Q000235:genetics; D013696:Temperature; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection
chemical_list: D017500:Adenovirus E1A Proteins; D000957:Antigens, Viral, Tumor; D018797:Cell Cycle Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D051863:Host Cell Factor C1; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D010750:Phosphoproteins; D011506:Proteins; D016160:Retinoblastoma Protein; D050717:Retinoblastoma-Like Protein p130; D014157:Transcription Factors