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Departments of Microbiology/Immunology and Pathology, Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107 [P. P. C., A. D. L., C. M. H., A. B., A. G.]; Department of Basic Science, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104 [E. J. F.]; Memorial Sloan-Kettering Cancer Center, New York, New York 10021 [A. K.], and Regina Elena Institute for Cancer Research, CRS 00158 Rome, Italy [M. G. P.]
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 G1 phase of the cell cycle. We demonstrated here that the growth-suppressive properties of pRb2/p130 were also specific for the G1 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 G1 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 G1-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 G1-S-phase regulator.
1 This work was supported by Sbarro Institute for Cancer Research and Molecular Medicine, NIH Grant RO1CA60999-01A1, and The Council for Tobacco Research (A. G.). P. P. C. was supported by a fellowship from the American-Italian Cancer Foundation. M. G. P. was supported by grants from Associazione Italiana per la Ricerca sul Cancro and Consiglio Nazionale delle Ricerche-Applicazioni Cliniche della Ricerca Oncologica.
2 On leave of absence from the Departments of Maxillo-Facial Surgery and Anatomic Pathology, School of Medicine, University of Naples "Federico II," Naples, Italy.
3 Recipient of an "Advanced Fellowship NATO-CNR".
4 Recipient of a United States (NIH)-Italy (Consiglio Nazionale delle Ricerche) Short-term Scientist Exchange Program fellowship.
5 To whom requests for reprints should be addressed, at Departments of Microbiology/Immunology and Pathology, Thomas Jefferson University, Philadelphia, PA 19107. Phone: (215) 503-0781; Fax: (215) 923-9626; E-mail: agiordan@lac.jci.tju.edu.
Received 2/14/96. Accepted 3/19/96.
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