Mitogenic and oncogenic properties of the small G protein rap1b
Mitogenic and oncogenic properties of the small G protein rap1b
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DOI：
10.1073/pnas.95.13.7475
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发表时间：
1998-06-23
影响因子：
11.1
通讯作者：
Ribeiro-Neto, F
中科院分区：
文献类型：
--
作者：
Altschuler, DL;Ribeiro-Neto, F
据广泛报道，小 GTP 结合蛋白 Rap1 具有抗 Ras 和抗有丝分裂活性，因此，人们普遍认为 Rap1 蛋白的正常生理作用是拮抗 Ras 有丝分裂信号，大概是通过与典型的 Ras 效应物或调节剂的蛋白质形成非生产性复合物，Rap1 被提高细胞内 cAMP 水平的信号激活，cAMP 是一种长期以来已知发挥抑制和刺激作用的分子关于细胞生长，我们现在已经测试了一个有趣的假设，即 Rap1 可能在 cAMP 刺激细胞增殖的系统中具有促有丝分裂作用。针对这种可能性的实验结果表明 Rap1 具有完全的致癌潜力。 Rap1 在这些细胞中的表达导致倍增时间缩短、饱和密度增加以及不寻常的锚定依赖性形态转变。然而，最重要的是，表达 Rap1 的细胞注射到裸鼠体内后形成了肿瘤。因此，我们建议应该限制Rap1作为抗有丝分裂蛋白的观点，并得出Rap1是条件癌蛋白的结论。
It has been widely reported that the small GTP-binding protein Rap1 has an anti-Ras and antimitogenic activity, Thus, it is generally accepted that a normal physiological role of Rap1 proteins is to antagonize Ras mitogenic signals, presumably by forming nonproductive complexes with proteins that are typically effecters or modulators of Ras, Rap1 is activated by signals that raise intracellular levels of cAMP, a molecule that has long been known to exert both inhibitory and stimulatory effects on cell growth,We have now tested the intriguing hypothesis that Rap1 could have mitogenic effects in systems in which cAMP stimulates cell proliferation. The result of experiments addressing this possibility revealed that Rap1 has full oncogenic potential. Expression of Rap1 in these cells results in a decreased doubling time, an increased saturation density, and an unusual anchorage-dependent morphological transformation. Most significantly, however, Rap1-expressing cells formed tumors when injected into nude mice. Thus, we propose that the view that holds Rap1 as an antimitogenic protein should be restricted and conclude that Rap1 is a conditional oncoprotein.