Beckner S K, Hattori S, Shih T Y
Nature. 1985;317(6032):71-2. doi: 10.1038/317071a0.
Harvey (Ha-MSV) and Kirsten (Ki-MSV) murine sarcoma viruses induce tumours in animals and transform various cells in culture because of the expression of the ras oncogene product, p21 (ref. 1). Proto-oncogenes homologous with these genes are highly conserved evolutionarily and activated ras oncogenes have been detected in many human cancers. Whether c-ras oncogenes are directly responsible for human carcinogenesis is uncertain; however, it is clear that p21 mediates virus-induced transformation, although by an unknown mechanism. Epithelial and fibroblast cell lines transformed with Ha-MSV and Ki-MSV express p21 (ref. 8) and exhibit reduced adenylate cyclase activity. Like the guanine nucleotide regulatory proteins, Ns and Ni, which mediate stimulation and inhibition, respectively, of adenylate cyclase, p21 is a membrane-associated GTP binding protein, which exhibits GTPase activity. These similarities suggest that p21 and the adenylate cyclase regulatory proteins are related in cellular function, and that p21 depresses adenylate cyclase by inhibiting the activity of Ns or acting as Ni. We have therefore now examined the structural and functional similarities between p21 and Ns and Ni and find no evidence that p21 regulates adenylate cyclase activity by acting as one of these regulatory proteins.
哈维（Ha-MSV）和 Kirsten（Ki-MSV）鼠肉瘤病毒可在动物体内诱发肿瘤，并在培养中转化各种细胞，这是由于癌基因产物 p21 的表达所致（参考文献 1）。与这些基因同源的原癌基因在进化上高度保守，并且在许多人类癌症中都检测到了激活的癌基因。c-ras 癌基因是否直接导致人类癌症尚不确定；然而，很明显 p21 介导病毒诱导的转化，尽管其机制尚不清楚。用 Ha-MSV 和 Ki-MSV 转化的上皮和成纤维细胞系表达 p21（参考文献 8）并表现出腺苷酸环化酶活性降低。与分别介导腺苷酸环化酶刺激和抑制的鸟嘌呤核苷酸调节蛋白 Ns 和 Ni 一样，p21 是一种与膜相关的 GTP 结合蛋白，具有 GTP 酶活性。这些相似性表明 p21 与腺苷酸环化酶调节蛋白在细胞功能上相关，并且 p21 通过抑制 Ns 的活性或作为 Ni 来抑制腺苷酸环化酶。因此，我们现在研究了 p21 与 Ns 和 Ni 之间的结构和功能相似性，并未发现 p21 通过作为这些调节蛋白之一来调节腺苷酸环化酶活性的证据。
