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Title: Caspase-3 is required in the apoptotic disintegration of the nuclear matrix

Abstract

Apoptotic breakdown of cellular structures is largely mediated by caspases. One target of degradation is a proteinaceous framework of the nucleus termed the nuclear matrix. We compared the apoptotic changes of the nuclear matrix in staurosporine-treated caspase-3-deficient MCF-7 cells transfected with intact CASP-3 gene (MCF-7c3) or an empty vector (MCF-7v) as a control. Nuclear Mitotic Apparatus protein (NuMA), lamin A/C and lamin B were used as markers for internal nuclear matrix and peripheral nuclear lamina, respectively. In both cell lines, staurosporine induced rapid cytoplasmic shrinkage and partial chromatin condensation. MCF-7c3 cells formed apoptotic bodies, whereas MCF-7v cells did not. NuMA and lamins were actively cleaved in MCF-7c3 cells following caspase-3 activation, but only minimal or no cleavage was detected in MCF-7v cells. Interestingly, lamin B but not lamin A/C was relocated into cytoplasmic granules in apoptotic MCF-7v cells. Pancaspase inhibitor, z-VAD-fmk, prevented the apoptotic changes, while caspase-3 inhibitor, z-DEVD-fmk, induced lamin B granules in both cell lines. These results show that caspase-3 is involved in the cleavage of NuMA and lamins either directly or by activating other proteases. This may be essential for disintegration of the nuclear structure during apoptosis.

Authors:
 [1];  [2];  [1];  [3]
  1. Department of Pathology, University of Turku, MediCity Research Laboratory, Tykistoekatu 6 A, 4th floor, FIN-20520 Turku (Finland)
  2. (Finland)
  3. Department of Pathology, University of Turku, MediCity Research Laboratory, Tykistoekatu 6 A, 4th floor, FIN-20520 Turku (Finland). E-mail: pekka.taimen@utu.fi
Publication Date:
OSTI Identifier:
20717686
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 311; Journal Issue: 1; Other Information: DOI: 10.1016/j.yexcr.2005.08.006; PII: S0014-4827(05)00383-6; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; CELL NUCLEI; CHROMATIN; CLEAVAGE; GENES; NUCLEAR STRUCTURE; PROTEINS

Citation Formats

Kivinen, Katri, Turku Graduate School of Biomedical Sciences, Turku, Kallajoki, Markku, and Taimen, Pekka. Caspase-3 is required in the apoptotic disintegration of the nuclear matrix. United States: N. p., 2005. Web. doi:10.1016/j.yexcr.2005.08.006.
Kivinen, Katri, Turku Graduate School of Biomedical Sciences, Turku, Kallajoki, Markku, & Taimen, Pekka. Caspase-3 is required in the apoptotic disintegration of the nuclear matrix. United States. doi:10.1016/j.yexcr.2005.08.006.
Kivinen, Katri, Turku Graduate School of Biomedical Sciences, Turku, Kallajoki, Markku, and Taimen, Pekka. Tue . "Caspase-3 is required in the apoptotic disintegration of the nuclear matrix". United States. doi:10.1016/j.yexcr.2005.08.006.
@article{osti_20717686,
title = {Caspase-3 is required in the apoptotic disintegration of the nuclear matrix},
author = {Kivinen, Katri and Turku Graduate School of Biomedical Sciences, Turku and Kallajoki, Markku and Taimen, Pekka},
abstractNote = {Apoptotic breakdown of cellular structures is largely mediated by caspases. One target of degradation is a proteinaceous framework of the nucleus termed the nuclear matrix. We compared the apoptotic changes of the nuclear matrix in staurosporine-treated caspase-3-deficient MCF-7 cells transfected with intact CASP-3 gene (MCF-7c3) or an empty vector (MCF-7v) as a control. Nuclear Mitotic Apparatus protein (NuMA), lamin A/C and lamin B were used as markers for internal nuclear matrix and peripheral nuclear lamina, respectively. In both cell lines, staurosporine induced rapid cytoplasmic shrinkage and partial chromatin condensation. MCF-7c3 cells formed apoptotic bodies, whereas MCF-7v cells did not. NuMA and lamins were actively cleaved in MCF-7c3 cells following caspase-3 activation, but only minimal or no cleavage was detected in MCF-7v cells. Interestingly, lamin B but not lamin A/C was relocated into cytoplasmic granules in apoptotic MCF-7v cells. Pancaspase inhibitor, z-VAD-fmk, prevented the apoptotic changes, while caspase-3 inhibitor, z-DEVD-fmk, induced lamin B granules in both cell lines. These results show that caspase-3 is involved in the cleavage of NuMA and lamins either directly or by activating other proteases. This may be essential for disintegration of the nuclear structure during apoptosis.},
doi = {10.1016/j.yexcr.2005.08.006},
journal = {Experimental Cell Research},
number = 1,
volume = 311,
place = {United States},
year = {Tue Nov 15 00:00:00 EST 2005},
month = {Tue Nov 15 00:00:00 EST 2005}
}