Del Sal G, Ruaro E M, Utrera R, Cole C N, Levine A J, Schneider C
Laboratorio Nazionale Consorzio Interuniversitario per le Biotecnologie, Trieste, Italy.
Mol Cell Biol. 1995 Dec;15(12):7152-60. doi: 10.1128/MCB.15.12.7152.
In normal cells, induction of quiescence is accompanied by the increased expression of growth arrest-specific genes (gas). One of them, gas1, is regulated at the transcriptional level and codes for a membrane-associated protein (Gas1) which is down regulated during the G0-to-S phase transition in serum-stimulated cells. Gas1 is not expressed in growing or transformed cells, and when overexpressed in normal fibroblasts, it blocks the G0-to-S phase transition. Moreover, Gas1 blocks cell proliferation in several transformed cells with the exception of simian virus 40- or adenovirus-transformed cell lines. In this paper, we demonstrate that overexpression of Gas1 blocks cell proliferation in a p53-dependent manner and that the N-terminal domain-dependent transactivating function of p53 is dispensable for Gas1-induced growth arrest. These data therefore indicate that the other intrinsic transactivation-independent functions of p53, possibly related to regulation of apoptosis, should be involved in mediating Gas1-induced growth arrest.
在正常细胞中，静止状态的诱导伴随着生长停滞特异性基因（gas）表达的增加。其中一个基因gas1在转录水平受到调控，编码一种膜相关蛋白（Gas1），该蛋白在血清刺激的细胞从G0期到S期转变过程中表达下调。Gas1在生长或转化细胞中不表达，当在正常成纤维细胞中过表达时，它会阻断从G0期到S期的转变。此外，Gas1可阻断多种转化细胞的增殖，但猿猴病毒40或腺病毒转化的细胞系除外。在本文中，我们证明Gas1的过表达以p53依赖的方式阻断细胞增殖，并且p53的N末端结构域依赖性反式激活功能对于Gas1诱导的生长停滞是可有可无的。因此，这些数据表明p53的其他内在的不依赖反式激活的功能，可能与细胞凋亡的调控有关，应该参与介导Gas1诱导的生长停滞。
