THE RAS ONCOGENE PRODUCT P21 IS NOT A REGULATORY COMPONENT OF ADENYLATE-CYCLASE
THE RAS ONCOGENE PRODUCT P21 IS NOT A REGULATORY COMPONENT OF ADENYLATE-CYCLASE
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DOI：
10.1038/317071a0
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发表时间：
1985-01-01
期刊：
影响因子：
64.8
通讯作者：
SHIH, TY
中科院分区：
文献类型：
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作者：
BECKNER, SK;HATTORI, S;SHIH, TY
Harvey（Ha-MSV）和Kirsten（Ki-MSV）鼠肉瘤病毒在动物体内诱发肿瘤，并由于癌基因产物p21的表达而转化培养物中的各种细胞（参考文献1）。与这些基因同源的原癌基因在进化上是高度保守的2，并且在许多人类癌症中检测到激活的原癌基因3 - 7。c-ras癌基因是否直接导致人类癌变尚不确定;然而，很明显p21介导病毒诱导的转化，尽管机制未知。Ha-MSV和Ki-MSV转化的上皮细胞和成纤维细胞系表达p21（参考文献8），并显示腺苷酸环化酶活性降低9，10。与分别介导腺苷酸环化酶的刺激11和抑制12的鸟嘌呤核苷酸调节蛋白N和Ni一样，p21是一种膜相关GTP结合蛋白，其表现出GTP酶活性13 - 15。这些相似性表明，p21和腺苷酸环化酶调节蛋白在细胞功能相关，并且p21通过抑制Nsor作为Ni的活性来抑制腺苷酸环化酶。因此，我们现在已经研究了p21和Nsand Ni之间的结构和功能相似性，没有发现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。
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 therasoncogene product, p21 (ref. 1). Proto-oncogenes homologous with these genes are highly conserved evolutionarily2and activatedrasoncogenes have been detected in many human cancers3–7. Whether c-rasoncogenes 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 activity9,10. Like the guanine nucleotide regulatory proteins, Nsand Ni, which mediate stimulation11and inhibition12, respectively, of adenylate cyclase, p21 is a membrane-associated GTP binding protein, which exhibits GTPase activity13–15. 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 Nsor acting as Ni. We have therefore now examined the structural and functional similarities between p21 and Nsand Niand find no evidence that p21 regulates adenylate cyclase activity by acting as one of these regulatory proteins.