JNK1, JNK2 and JNK3 are p53 N-terminal serine 34 kinases
JNK1, JNK2 and JNK3 are p53 N-terminal serine 34 kinases
复制标题
DOI：
10.1038/sj.onc.1201401
复制
发表时间：
1997-11-06
期刊：
影响因子：
8
通讯作者：
Wang, YP
中科院分区：
文献类型：
--
作者：
Hu, MCT;Qiu, WR;Wang, YP
肿瘤抑制蛋白P53的功能受翻译后事件的调节，主要是通过磷酸化。根据细胞环境的不同，P53在多个位置被不同的蛋白激酶磷酸化。有研究表明，小鼠P53的丝氨酸34被应激激活的蛋白激酶特异性地磷酸化，以响应紫外线辐射。由于丝氨酸34是小鼠P53在体内的主要磷酸化部位，其特异性蛋白激酶尚未确定，我们通过在293T细胞中表达JNK1，检测了c-Jun氨基末端激酶1(JNK1)在P53上的活性。在体外，我们发现激活的JNK1能特异性地磷酸化小鼠P53的丝氨酸34位，而显性阴性的JNK1突变体不能磷酸化P53。更重要的是，JNK1在活体内与P53结合，无论激活与否，证实了JNK1确实是一种P53激酶。有趣的是，激活的JNK2和JNK3也使小鼠P53的丝氨酸34磷酸化。此外，JNK2和JNK3在体内也与P53结合，表明不仅JNK1，而且JNK2和JNK3都是P53 N末端丝氨酸34激酶。JNKs对P53的磷酸化可能在响应环境应激或致癌物质的核信号转导中发挥重要作用。
The function of the tumor suppressor protein p53 is modulated by post-translational events, primarily by phosphorylation. p53 is phosphorylated at multiple sites by a variety of protein kinases depending on the cellular environment. It has been suggested that serine 34 of mouse p53 is specifically phosphorylated by a stress-activated protein kinase in response to ultraviolet radiation. Since serine 34 is a major site of phosphorylation of mouse p53 in vivo and its specific protein kinase is still not definitively identified yet, we have examined the c-Jun N-terminal kinase 1 (JNK1) activity on p53 by expressing JNK1 in 293T cells. We show here that activated JNK1 phosphorylates mouse p53 specifically at serine 34 in vitro, while a dominanant-negative JNK1 mutant does not phosphorylate p53. More importantly, JNK1 associates with p53 in vivo, with or without activation, confirming that JNK1 is indeed a p53 kinase. Interestingly, activated JNK2 and JNK3 also phosphorylate serine 34 of mouse p53. Furthermore, JNK2 and JNK3 also associate with p53 in vivo, indicating that not only JNK1, but also JNK2 and JNK3 are p53 N-terminal serine 34 kinases. Phosphorylation of p53 by JNKs may play an important role in nuclear signal transduction in response to environmental stress or tumorigenic agents.