Volume 20, No 2, Feb 2010
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 20 Issue 2, February 2010: 211-222
ORIGINAL ARTICLES
Nuclear entry of active caspase-3 is facilitated by its p3-recognition-based specific cleavage activity
Min Luo1,*, Zhiyong Lu1,2,*, He Sun1, Kehu Yuan1, Quancang Zhang1, Sha Meng1, Fangxun Wang1, Hongchun Guo1, Xiaofang Ju1, Yuqing Liu3, Tao Ye1,3, Zhigang Lu1 and Zhonghe Zhai4
1Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School of Peking University, Shenzhen 518055, China;
2Institute of Life Sciences, YunYang Medical College Tai-he Hospital, 32 S Renmin Road, Shiyan, Hubei 442000, China;
3Department of Applied Biology & Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong;
4College of Life Science, Peking University, Beijing 100871, China
Correspondence: Zhigang Lu,(luzg@szpku.edu.cn )
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.
Cell Research (2010) 20:211-222. doi: 10.1038/cr.2010.9; published online 26 January 2010
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