Caspase-6 gene disruption reveals a requirement for lamin A cleavage in apoptotic chromatin condensation

AUTOR(ES)

Ruchaud, Sandrine

FONTE

Oxford University Press

RESUMO

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.

Documentos Relacionados

• Apoptotic threshold is lowered by p53 transactivation of caspase-6
• Caspase cleavage of MST1 promotes nuclear translocation and chromatin condensation
• Critical loss of CBP/p300 histone acetylase activity by caspase-6 during neurodegeneration
• Caspase cleavage of BimEL triggers a positive feedback amplification of apoptotic signaling
• Caspase-mediated Cleavage of p130cas in Etoposide-induced Apoptotic Rat-1 Cells