D4-GDI, a Substrate of CPP32, Is Proteolyzed during Fas-induced Apoptosis
In: Journal of Biological Chemistry, Jg. 271 (1996-05-01), S. 11209-11213
Online
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Zugriff:
Apoptosis (programmed cell death) is a fundamental process for normal development of multicellular organisms, and is involved in the regulation of the immune system, normal morphogenesis, and maintenance of homeostasis, ICE/CED-3 family cysteine proteases have been implicated directly in apoptosis, but relatively few of the substrates through which their action is mediated have been identified. Here we report that D4-GDI, an abundant hematopoietic cell GDP dissociation inhibitor for the Ras-related Rho family GTPases, is a substrate of the apoptosis protease CPP32/Yama/Apopain. D4-GDI was rapidly truncated to a 23-kDa fragment in Jurkat cells with kinetics that parallel the onset of apoptosis following Fas cross-linking with agonistic antibody or treatment with staurosporine. Fas- and staurosporine-induced apoptosis as well as cleavage of D4-GDI were inhibited by the ICE inhibitor, YVAD-cmk. D4-GDI was cleaved in vitro by recombinant CPP32 expressed in Escherichia coli to form a 23-kDa fragment. The CPP32-mediated cleavage of D4-GDI was completely inhibited by 1 microM DEVD-CHO, a reported selective inhibitor of CPP32. In contrast, the ICE-selective inhibitors, YVAD-CHO or YVAD-cmk, did not inhibit CPP32-mediated D4-GDI cleavage at concentrations up to 50 microM. N-terminal sequencing of the 23-kDa D4-GDI fragment demonstrated that D4-GDI was cleaved between Asp19 and Ser20 of the poly(ADP-ribose) polymerase-like cleavage sequence DELD19S. These data suggest that regulation by D4-GDI of Rho family GTPases may be disrupted during apoptosis by CPP32-mediated cleavage of the GDI protein.
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D4-GDI, a Substrate of CPP32, Is Proteolyzed during Fas-induced Apoptosis
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Autor/in / Beteiligte Person: | Turi, Thomas G. ; Na, Songqing ; Cunningham, Ann C. ; Jeffrey Herbert Hanke ; Danley, Dennis E. ; Bokoch, Gary M. ; Chuang, Tsung-Hsien |
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Zeitschrift: | Journal of Biological Chemistry, Jg. 271 (1996-05-01), S. 11209-11213 |
Veröffentlichung: | Elsevier BV, 1996 |
Medientyp: | unknown |
ISSN: | 0021-9258 (print) |
DOI: | 10.1074/jbc.271.19.11209 |
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