Specific cleavage of the large subunit of replication factor C in apoptosis is mediated by CPP32-like protease.
Recent evidence suggests that the growing family of cysteine proteases related to the interleukin-1beta-converting enzyme (ICE) is of central importance in mediating apoptosis. Proteolytic cleavage of a small group of cellular substrates by these enzymes in association with the onset of apoptosis has been reported. In the present study, we searched a protein data base for potential death substrates possessing the CPP32 cleavage site, DEVD, and identified several candidates including RFC140, the large subunit of replication factor C, which we subsequently demonstrated to be specifically cleaved in a variety of cell types undergoing apoptosis in response to different cytotoxic agents, whereas no degradation is observed in a cell line resistant to etoposide-induced apoptosis. The abrogation of RFC140 cleavage in apoptotic extracts by Ac-DEVD-CHO, a potent inhibitor of CPP32, together with the finding that a CPP32 consensus cleavage sequence, DEVD, exists in RFC140, suggests that CPP32 or a close relative is responsible for RFC140 degradation in apoptosis.
Song
Q
Q
Queensland Institute of Medical Research, University of Queensland, P.O. Royal Brisbane Hospital, Australia. qizhongS@qimr.edu.au
Lu
H
H
Zhang
N
N
Luckow
B
B
Shah
G
G
Poirier
G
G
Lavin
M
M
D000818:Animals; D017209:Apoptosis; D020170:Caspase 1; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004792:Enzyme Precursors / Q000378:metabolism; D018398:Homeodomain Proteins; D007375:Interleukin-1 / Q000378:metabolism; D015778:Minor Histocompatibility Antigens; D009842:Oligopeptides / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051818:Replication Protein C; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014407:Tumor Cells, Cultured
C096816:BCL2-related protein A1; D015853:Cysteine Proteinase Inhibitors; D004268:DNA-Binding Proteins; D004792:Enzyme Precursors; D018398:Homeodomain Proteins; D007375:Interleukin-1; C096063:MATA1 protein, S cerevisiae; D015778:Minor Histocompatibility Antigens; D009842:Oligopeptides; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C099158:acetyl-aspartyl-glutamyl-valyl-aspartal; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases; D020170:Caspase 1; D051818:Replication Protein C