Dissociation of retinoblastoma gene protein hyperphosphorylation and commitment to enter S phase.
Mitogenic activities of simian virus 40 large T and small t antigens were studied in serum-deprived human diploid fibroblasts. Wild-type large T and small t cooperated in stimulating DNA synthesis and in inducing hyperphosphorylation of the Rb gene product (pRb). In contrast, a T antigen mutant defective for pRb binding (Rb- T) possessed no detectable mitogenic activity alone and failed to complement small t in stimulating DNA synthesis. Surprisingly, Rb- T and small t cooperated as strongly as wild-type T and small t with respect to pRb hyperphosphorylation. As a consequence, in two closely related conditions (i.e., stimulation by small t plus wild-type T versus small t plus Rb- T), the fraction of pRb in hyperphosphorylated forms dissociated from the fraction of cells in the S phase. These results indicate that pRb hyperphosphorylation is not always tightly coupled with a commitment to initiate DNA replication.
Ogryzko
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Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, Bethesda, Maryland 20892.
Hirai
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TH
Shih
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CE
Howard
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BH
D000952:Antigens, Polyomavirus Transforming / Q000235:genetics / Q000378:metabolism; D002087:Butyrates / Q000494:pharmacology; D020148:Butyric Acid; D002460:Cell Line; D004261:DNA Replication / Q000502:physiology; D006801:Humans; D008934:Mitogens; D010766:Phosphorylation; D016160:Retinoblastoma Protein / Q000378:metabolism*; D016196:S Phase / Q000502:physiology*; D014162:Transfection
D000952:Antigens, Polyomavirus Transforming; D002087:Butyrates; D008934:Mitogens; D016160:Retinoblastoma Protein; D020148:Butyric Acid