Nuclear entry of active caspase-3 is facilitated by its p3-recognition-based specific cleavage activity

Min Luo, Zhiyong Lu, He Sun, Kehu Yuan, Quancang Zhang, Sha Meng, Fangxun Wang, Hongchun Guo, Xiaofang Ju, Yuqing Liu, Tao Ye, Zhigang Lu, Zhonghe Zhai

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29 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)211-222
Number of pages12
JournalCell Research
Issue number2
Publication statusPublished - Feb 1 2010



  • Apoptosis
  • Caspase-3
  • Nuclear entry
  • Nuclear export signal

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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