Functional analysis of pRb2/p130 interaction with cyclins

Claudio, P.P.; De Luca, A.; Howard, C.M.; Baldi, A.; Firpo, E.J.; Koff, A.; Paggi, M.G.; Giordano, A.

Cancer Research 56(9): 2003-2008

1996


ISSN/ISBN: 0008-5472
PMID: 8616840
Document Number: 460289
The retinoblastoma (Rb) family consists of the tumor suppressor pRb and related proteins p107 and pRb2/p130. Ectopic expression of pRb and p107 results in a growth arrest of sensitive cells in the G-1 phase of the cell cycle. We demonstrated here that the growth-suppressive properties of pRb2/p130 were also specific for the G-1 phase. The A-, E-, and D-type cyclins as well as transcription factor E2F1 and the E1A viral oncoprotein were able to rescue the pRb2/p130-mediated G-1 growth arrest in SAOS-2 cells. The rescue with cyclins A and E correlated with their physical interaction with pRb2/p130, which surprisingly has been found to occur over all phases of the cell cycle. The phosphorylation status as well as the kinase activity associated with pRb2/p130 dramatically increased near the G-1-S-phase transition. This suggests that, like the other Rb family members, pRb and p107, the phosphorylation of pRb2/p130 is controlled by the cell cycle machinery and that pRb2/p130 may indeed be another key G-1-S-phase regulator.

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