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.
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Abbreviations
- rev-caspase-3:
-
(reverse-caspase-3)
- NES:
-
(nuclear export signal)
- NLS:
-
(nuclear localization signal)
- LMB:
-
(leptomycin B)
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Acknowledgements
We thank Prof Jian Wang (Shanghai University, Shanghai) for his valuable revision and discussion. This work was supported by grants from the National Natural Science Foundation of China (30700411), Shenzhen Bureau of Science Technology and Information (SZKJ-2006018, SZKJ-2007012), Shenzhen Nanshan Bureau of Science Technology and Information (2008036) and Shenzhen Key Laboratory Advancement Scheme.
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Supplementary information
Supplementary information, Figure S1
Analysis of the apoptosis inducing activities of Rev-caspase3 and its mutants. (PDF 14 kb)
Supplementary information, Figure S2
Lamin B1 and PARP were specifically cleaved by the wild type Rev-caspase3 (PDF 26 kb)
Supplementary information, Table S1
Table Cellular localization of Rev-caspase3 mutants (PDF 14 kb)
Supplementary information, Data S1
Amino acid sequence of Rev-caspase3. (PDF 10 kb)
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Luo, M., Lu, Z., Sun, H. et al. Nuclear entry of active caspase-3 is facilitated by its p3-recognition-based specific cleavage activity. Cell Res 20, 211–222 (2010). https://doi.org/10.1038/cr.2010.9
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DOI: https://doi.org/10.1038/cr.2010.9
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