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

Research output: Contribution to journalArticle

29 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)211-222
Number of pages12
JournalCell Research
Volume20
Issue number2
DOIs
StatePublished - Feb 1 2010

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Caspase 3
Nuclear Export Signals
Apoptosis
Mutation

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

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

In: Cell Research, Vol. 20, No. 2, 01.02.2010, p. 211-222.

Research output: Contribution to journalArticle

Luo, M, Lu, Z, Sun, H, Yuan, K, Zhang, Q, Meng, S, Wang, F, Guo, H, Ju, X, Liu, Y, Ye, T, Lu, Z & Zhai, Z 2010, 'Nuclear entry of active caspase-3 is facilitated by its p3-recognition-based specific cleavage activity', Cell Research, vol. 20, no. 2, pp. 211-222. https://doi.org/10.1038/cr.2010.9
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. / Nuclear entry of active caspase-3 is facilitated by its p3-recognition-based specific cleavage activity. In: Cell Research. 2010 ; Vol. 20, No. 2. pp. 211-222.
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AU - Meng, Sha

AU - Wang, Fangxun

AU - Guo, Hongchun

AU - Ju, Xiaofang

AU - Liu, Yuqing

AU - Ye, Tao

AU - Lu, Zhigang

AU - Zhai, Zhonghe

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N2 - 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.

AB - 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.

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