Caspase-6 gene disruption reveals a requirement for lamin A cleavage in apoptotic chromatin condensation
Open Access
- 15 April 2002
- journal article
- research article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 21 (8), 1967-1977
- https://doi.org/10.1093/emboj/21.8.1967
Abstract
To study the role of caspase‐6 during nuclear disassembly, we generated a chicken DT40 cell line in which both alleles of the caspase‐6 gene were disrupted. No obvious morphological differences were observed in the apoptotic process in caspase‐6‐ deficient cells compared with the wild type. However, examination of apoptosis in a cell‐free system revealed a block in chromatin condensation and apoptotic body formation when nuclei from HeLa cells expressing lamin A or lamin A‐transfected Jurkat cells were incubated in caspase‐6‐deficient apoptotic extracts. Transfection of exogenous caspase‐6 into the clone reversed this phenotype. Lamins A and C, which are caspase‐6‐only substrates, were cleaved by the wild‐type and heterozygous apoptotic extracts but not by the extracts lacking caspase‐6. Furthermore, the caspase‐6 inhibitor z‐VEID‐fmk mimicked the effects of caspase‐6 deficiency and prevented the cleavage of lamin A. Taken together, these observations indicate that caspase‐6 activity is essential for lamin A cleavage and that when lamin A is present it must be cleaved in order for the chromosomal DNA to undergo complete condensation during apoptotic execution.Keywords
This publication has 70 references indexed in Scilit:
- Transcription Factor AP-2α Is Preferentially Cleaved by Caspase 6 and Degraded by Proteasome during Tumor Necrosis Factor Alpha-Induced Apoptosis in Breast Cancer CellsMolecular and Cellular Biology, 2001
- SATB1 Cleavage by Caspase 6 Disrupts PDZ Domain-Mediated Dimerization, Causing Detachment from Chromatin Early in T-Cell ApoptosisMolecular and Cellular Biology, 2001
- LMNA, encoding lamin A/C, is mutated in partial lipodystrophyNature Genetics, 2000
- Pushing the envelope on lipodystrophyNature Genetics, 2000
- MAN1, an Inner Nuclear Membrane Protein That Shares the LEM Domain with Lamina-associated Polypeptide 2 and EmerinJournal of Biological Chemistry, 2000
- Direct Interaction between Emerin and Lamin ABiochemical and Biophysical Research Communications, 2000
- Comparison of Paclitaxel-, 5-Fluoro-2′-deoxyuridine-, and Epidermal Growth Factor (EGF)-induced ApoptosisPublished by Elsevier BV ,1999
- Mitotic chromatin condensation in vitro using somatic cell extracts and nuclei with variable levels of endogenous topoisomerase II.The Journal of cell biology, 1990
- Differential accessibility of the tail domain of nuclear lamin A in interphase and mitotic cellsBiochemical and Biophysical Research Communications, 1990
- On the cell-free association of lamins A and C with metaphase chromosomesExperimental Cell Research, 1990