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

Cell Research
Min LuoZhonghe Zhai

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.

References

Jul 1, 1996·Nature Structural Biology·J RotondaJ W Becker
May 30, 1998·The Journal of Biological Chemistry·S M SrinivasulaE S Alnemri
Dec 28, 1999·Annual Review of Cell and Developmental Biology·I BudihardjoX Wang
Jun 29, 2000·Annual Review of Biochemistry·W C EarnshawS H Kaufmann
Nov 22, 2000·The Journal of Cell Biology·L Faleiro, Y Lazebnik
Aug 23, 2001·Proceedings of the National Academy of Sciences of the United States of America·S UraY Gotoh
Jun 5, 2002·The Journal of Cell Biology·Michael MorganAndrew Thorburn
Sep 18, 2002·The Journal of Cell Biology·Justine C LeeMarcus E Peter
Nov 5, 2002·Annual Review of Immunology·Vanessa S Marsden, Andreas Strasser
Jan 7, 2003·The Journal of Biological Chemistry·Nan-Shan ChangAmy Ensign
Jan 16, 2003·The Journal of Cell Biology·Kiwamu TakemotoMasayuki Miura
Mar 26, 2003·Cell Death and Differentiation·U FischerK Schulze-Osthoff
Apr 17, 2003·Molecular and Cellular Biology·David García-DomingoCarlos Martínez-A
May 7, 2004·The Journal of Biological Chemistry·Jae J Song, Yong J Lee
Feb 10, 2007·International Journal of Cancer. Journal International Du Cancer·Lindsey J GrayC Simon Herrington
Jun 17, 2008·Nature Cell Biology·Nilkantha SenAkira Sawa

❮ Previous
Next ❯

Citations

Sep 2, 2014·Developmental Biology·Danhua ZhangP Duc Si Dong
Sep 3, 2011·Molecular Reproduction and Development·Ana Rita S CoutinhoVilceu Bordignon
Jul 31, 2014·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·D WangL S Teng
Jul 25, 2018·Biotechnic & Histochemistry : Official Publication of the Biological Stain Commission·S KayacanM Ozturk
Mar 29, 2014·ChemMedChem·Hsueh-Liang ChuChia-Ching Chang
Sep 21, 2017·MBio·Sarah N CroftReena Ghildyal
Mar 13, 2014·Infection and Immunity·Christopher R DoyleDavid G Thanassi
Oct 22, 2014·International Journal of Oncology·Sze-Kwan LamJames Chung-Man Ho
Aug 17, 2018·Scientific Reports·Evgeniia A ProkhorovaBoris Zhivotovsky
Sep 2, 2014·International Journal of Oncology·Sze-Kwan LamJames Chung-Man Ho
Jun 28, 2018·Cell Proliferation·Gelina S KopeinaBoris Zhivotovsky
Mar 20, 2019·Neurochemical Research·Wilasinee SuwanjangKomgrid Charngkaew
Aug 8, 2020·Apoptosis : an International Journal on Programmed Cell Death·Debbra Y KnorrRalf Heinrich
Aug 14, 2020·Bioconjugate Chemistry·Linlin YangIvan J Dmochowski

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis