Zhu L, van den Heuvel S, Helin K, Fattaey A, Ewen M, Livingston D, Dyson N, Harlow E
Massachusetts General Hospital Cancer Center, Charlestown 02129.
Genes Dev. 1993 Jul;7(7A):1111-25. doi: 10.1101/gad.7.7a.1111.
The cellular protein p107 shares many structural and biochemical features with the retinoblastoma gene product, pRB. We have isolated a full-length cDNA for human p107 and have used this clone to study the function of p107. We show that, like pRB, p107 is a potent inhibitor of E2F-mediated trans-activation, and overexpression of p107 can inhibit proliferation in certain cell types, arresting sensitive cells in G1. Several experiments, however, showed that growth inhibition by pRB and p107 did not occur through the same mechanism. First, in the cervical carcinoma cell line C33A, p107 was able to block cell proliferation, whereas pRB could not, even though both proteins were potent inhibitors of E2F-mediated transcription in this cell line. Second, growth arrest by pRB and p107 was rescued differentially by various cell cycle regulators. Third, some mutants of p107 that cannot associate with adenovirus E1A were still able to inhibit cell proliferation, whereas analogous mutants in pRB are known to be unable to block cell growth. Together, these results suggest a biological role of p107 that is related, but not identical, to that of pRB.
细胞蛋白p107与视网膜母细胞瘤基因产物pRB具有许多结构和生化特征。我们分离出了人p107的全长cDNA，并利用该克隆研究p107的功能。我们发现，与pRB一样，p107是E2F介导的反式激活的有效抑制剂，p107的过表达可抑制某些细胞类型的增殖，使敏感细胞停滞在G1期。然而，多项实验表明，pRB和p107对生长的抑制作用并非通过相同机制。首先，在宫颈癌细胞系C33A中，p107能够阻断细胞增殖，而pRB则不能，尽管这两种蛋白在此细胞系中都是E2F介导转录的有效抑制剂。其次，pRB和p107引起的生长停滞可被各种细胞周期调节因子不同程度地挽救。第三，一些不能与腺病毒E1A结合的p107突变体仍能抑制细胞增殖，而pRB中的类似突变体则已知无法阻断细胞生长。这些结果共同表明，p107的生物学作用与pRB相关，但并不相同。
