In vivo phosphorylation of poly(ADP‐ribose) polymerase is independent of its activation

FEBS Letters

Shimotohno, Kunitada³  Hatanaka, Masakazu³  Copeland, Terry D¹  Noda, Makoto²  Ariumi, Yasuo³  Masutani, Mitsuko⁴  Ueda, Kunihiro⁵ 

[1] ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, MD 21702, USA;Department of Molecular Oncology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan;Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan;Biochemistry Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan;Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan

关键词: Poly(ADP-ribose) polymerase;    Poly(ADP-ribosyl)ation;    Auto-modification;    Phosphorylation;    Serine kinase;    Apoptosis;   

DOI  :  10.1016/S0014-5793(98)01144-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme, which is activated by DNA strand breaks. Although PARP is known to be cleaved by the cysteine protease, caspase-3/CPP32, during apoptosis, signal cascade which regulates the PARP activity has not been fully understood. In this study, we investigated post-translational modification of PARP. We found that PARP was phosphorylated by a serine kinase in vivo. PARP was activated temporarily and extensive auto-modification occurred on PARP, possibly by the fragmented DNA during apoptosis induced by etoposide in Jurkat cells. However, the phosphorylation level was not changed for up to 6 h, after PARP cleavage began in apoptosis by the treatment with etoposide. Furthermore, we showed the presence of a PARP-associated kinase in nuclear extracts of the HTLV-I infected T-cell lines but not in uninfected T-cell lines, whereas this kinase did not inhibit the PARP activity even in the presence of ATP. Taken together, in vivo phosphorylation of PARP might be independent of the activation or cleavage of PARP.

【 授权许可】

Unknown