Amar S, Glozman A, Chung D, Adler V, Ronai Z, Friedman F K, Robinson R, Brandt-Rauf P, Yamaizumi Z, Pincus M R
Department of Pathology and Laboratory Medicine, Veterans Affairs Medical Center, Brooklyn, NY 11209, USA.
Cancer Chemother Pharmacol. 1997;41(1):79-85. doi: 10.1007/s002800050711.
We have obtained evidence that oncogenic and activated normal ras-p21 proteins utilize overlapping but distinct signal transduction pathways. Recently, we found that ras-p21 binds to both jun and its kinase, jun kinase (JNK). We now present evidence that suggests that oncogenic but not normal activated p21 depends strongly on early activation of JNK/jun. This early activation most likely involves direct interaction between oncogenic p21 and JNK/jun because p21 peptides that blocked the binding of p21 to JNK and jun strongly inhibited oncogenic p21-induced oocyte maturation while they did not inhibit insulin-activated normal cellular p21-induced maturation. Very similar results were also obtained for a newly characterized specific inhibitor of JNK which blocked oncogenic but not normal activated p21-induced oocyte maturation. We also found that both jun and JNK strongly enhanced oncogenic p21-induced oocyte maturation while they inhibited insulin-activated normal p21-induced oocyte maturation. These results suggest that the peptides and JNK inhibitor may be useful agents in selectively blocking the effects of oncogenic but not normal p21 in cells.
我们已经获得证据表明，致癌性和活化的正常ras-p21蛋白利用重叠但不同的信号转导途径。最近，我们发现ras-p21与jun及其激酶jun激酶（JNK）都结合。我们现在提供的证据表明，致癌性而非正常活化的p21强烈依赖于JNK/jun的早期激活。这种早期激活很可能涉及致癌性p21与JNK/jun之间的直接相互作用，因为阻断p21与JNK和jun结合的p21肽强烈抑制致癌性p21诱导的卵母细胞成熟，而它们并不抑制胰岛素激活的正常细胞p21诱导的成熟。对于一种新鉴定的JNK特异性抑制剂也获得了非常相似的结果，该抑制剂阻断致癌性而非正常活化的p21诱导的卵母细胞成熟。我们还发现，jun和JNK都强烈增强致癌性p21诱导的卵母细胞成熟，而它们抑制胰岛素激活的正常p21诱导的卵母细胞成熟。这些结果表明，这些肽和JNK抑制剂可能是在细胞中选择性阻断致癌性而非正常p21作用的有用试剂。
