Claudio P P, De Luca A, Howard C M, Baldi A, Firpo E J, Koff A, Paggi M G, Giordano A
Department of Microbiology-Immunology, Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Cancer Res. 1996 May 1;56(9):2003-8.
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.
视网膜母细胞瘤（Rb）家族由肿瘤抑制因子pRb以及相关蛋白p107和pRb2/p130组成。pRb和p107的异位表达导致敏感细胞在细胞周期的G1期生长停滞。我们在此证明，pRb2/p130的生长抑制特性也对G1期具有特异性。A、E和D型细胞周期蛋白以及转录因子E2F1和E1A病毒癌蛋白能够挽救SAOS-2细胞中pRb2/p130介导的G1期生长停滞。细胞周期蛋白A和E的挽救作用与其与pRb2/p130的物理相互作用相关，令人惊讶的是，这种相互作用在细胞周期的所有阶段都存在。与pRb2/p130相关的磷酸化状态以及激酶活性在G1-S期转变附近显著增加。这表明，与其他Rb家族成员pRb和p107一样，pRb2/p130的磷酸化受细胞周期机制控制，并且pRb2/p130可能确实是另一个关键的G1-S期调节因子。
