Title | Nuclear entry of active caspase-3 is facilitated by its p3-recognition-based specific cleavage activity |
Authors | Luo, Min Lu, Zhiyong Sun, He Yuan, Kehu Zhang, Quancang Meng, Sha Wang, Fangxun Guo, Hongchun Ju, Xiaofang Liu, Yuqing Ye, Tao Lu, Zhigang Zhai, Zhonghe |
Affiliation | Peking Univ, Lab Chem Genom, Sch Chem Biol & Biotechnol, Shenzhen Grad Sch, Shenzhen 518055, Peoples R China. Tai He Hosp, YunYang Med Coll, Inst Life Sci, Shiyan 442000, Hubei, Peoples R China. Hong Kong Polytech Univ, Dept Appl Biol & Chem Technol, Kowloon, Hong Kong, Peoples R China. Peking Univ, Coll Life Sci, Beijing 100871, Peoples R China. |
Keywords | nuclear entry caspase-3 apoptosis nuclear export signal CHROMATIN CONDENSATION LEPTOMYCIN-B APOPTOSIS ACTIVATION TRANSLOCATION SUBSTRATE EXPORT DEGRADATION GENERATION INHIBITOR |
Issue Date | 2010 |
Publisher | 细胞研究英文版 |
Citation | CELL RESEARCH.2010,20,(2),211-222. |
Abstract | As a critical apoptosis executioner, caspase-3 becomes activated and then enters into the nucleus to exert its function. However, the molecular mechanism of this nuclear entry of active caspase-3 is still unknown. In this study, we revealed that caspase-3 harbors a crm-1-independent nuclear export signal (NES) in its small subunit. Using reverse-caspase-3 as the study model, we found that the function of the NES in caspase-3 was not disturbed by the conformational changes during induced caspase-3 activation. Mutations disrupting the cleavage activity or p3-recognition site resulted in a defect in the nuclear entry of active caspase-3. We provide evidence that the p3-mediated specific cleavage activity of active caspase-3 abrogated the function of the NES. In conclusion, our results demonstrate that during caspase-3 activation, NES is constitutively present. p3-mediated specific cleavage activity abrogates the NES function in caspase-3, thus facilitating the nuclear entry of active caspase-3. |
URI | http://hdl.handle.net/20.500.11897/344883 |
ISSN | 1001-0602 |
DOI | 10.1038/cr.2010.9 |
Indexed | SCI(E) PubMed 中国科技核心期刊(ISTIC) 中国科学引文数据库(CSCD) |
Appears in Collections: | 化学生物学与生物技术学院 生命科学学院 |