FUNCTIONAL-ANALYSIS OF PRB2 P130 INTERACTION WITH CYCLINS/

The retinoblastoma (Rb) family consists of the tumor suppressor pRb an d related proteins p107 and pRb2/p130, Ectopic expression of pRb and p 107 results in a growth arrest of sensitive cells in the G(1) phase of the cell cycle, We demonstrated here that the growth-suppressive prop erties 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 EIA v iral oncoprotein were able to rescue the pRb2/p130-mediated G(1) growt h arrest in SAOS-2 cells. The rescue with cyclins A and E correlated w ith their physical interaction with pRb2/p130, which surprisingly has been found to occur over all phases of the cell cycle, The phosphoryla tion status as well as the kinase activity associated with pRb2/p130 d ramatically increased near the G(1)-S-phase transition, This suggests that, like the other Rb family members, pRb and p107, the phosphorylat ion of pRb2/p130 is controlled by the cell cycle machinery and that pR b2/p130 may indeed be another key G(1)-S-phase regulator.