JNK1, JNK2 AND JNK3 ARE P53 N-TERMINAL SERINE-34 KINASES

The function of the tumor suppressor protein p53 is modulated by post- translational events, primarily by phosphorylation. p53 is phosphoryla ted at multiple sites by a variety of protein kinases depending on the cellular environment. It has been suggested that serine 34 of mouse p 53 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 kina se is still not definitively identified yet, we have examined the c-Ju n N-terminal kinase 1 (JNK1) activity on p53 by expressing JNK1 in 293 T cells. We show here that activated JNK1 phosphorylates mouse p53 spe cifically at serine 34 in vitro, while a dominanant-negative JNK1 muta nt does not phosphorylate p53. More importantly, JNK1 associates with p53 in vivo, with or without activation, confirming that JNK1 is indee d a p53 kinase. Interestingly, activated JNK2 and JNK3 also phosphoryl ate serine 34 of mouse p53. Furthermore, JNK2 and JNK3 also associate with p53 in vivo, indicating that not only JNK1, but also JNK2 and JNK 3 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.