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. 1994 Jun;68(6):3724–3732. doi: 10.1128/jvi.68.6.3724-3732.1994

Dissociation of retinoblastoma gene protein hyperphosphorylation and commitment to enter S phase.

V V Ogryzko 1, T H Hirai 1, C E Shih 1, B H Howard 1
PMCID: PMC236877  PMID: 8189510

Abstract

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.

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Selected References

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