Publication Date:
1997-10-10
Description:
The caspase-3 (CPP32, apopain, YAMA) family of cysteinyl proteases has been implicated as key mediators of apoptosis in mammalian cells. Gelsolin was identified as a substrate for caspase-3 by screening the translation products of small complementary DNA pools for sensitivity to cleavage by caspase-3. Gelsolin was cleaved in vivo in a caspase-dependent manner in cells stimulated by Fas. Caspase-cleaved gelsolin severed actin filaments in vitro in a Ca2+-independent manner. Expression of the gelsolin cleavage product in multiple cell types caused the cells to round up, detach from the plate, and undergo nuclear fragmentation. Neutrophils isolated from mice lacking gelsolin had delayed onset of both blebbing and DNA fragmentation, following apoptosis induction, compared with wild-type neutrophils. Thus, cleaved gelsolin may be one physiological effector of morphologic change during apoptosis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kothakota, S -- Azuma, T -- Reinhard, C -- Klippel, A -- Tang, J -- Chu, K -- McGarry, T J -- Kirschner, M W -- Koths, K -- Kwiatkowski, D J -- Williams, L T -- P01 HL48743/HL/NHLBI NIH HHS/ -- R01 HL54188/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1997 Oct 10;278(5336):294-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Chiron Corporation, Emeryville, CA 94608, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9323209" target="_blank"〉PubMed〈/a〉
Keywords:
Actins/metabolism
;
Amino Acid Chloromethyl Ketones/pharmacology
;
Animals
;
Antigens, CD95/physiology
;
*Apoptosis
;
Caspase 3
;
*Caspases
;
Cell Line
;
*Cell Size
;
Cycloheximide/pharmacology
;
Cysteine Endopeptidases/*metabolism
;
Cysteine Proteinase Inhibitors/pharmacology
;
Cytoskeleton/metabolism
;
DNA Fragmentation
;
Gelsolin/*metabolism
;
Humans
;
Mice
;
Neutrophils/cytology/metabolism
;
Recombinant Proteins/metabolism
;
Transfection
;
Tumor Cells, Cultured
;
Tumor Necrosis Factor-alpha/pharmacology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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