Publication Date:
2000-05-08
Description:
To determine why proteasome inhibitors prevent thymocyte death, we examined whether proteasomes degrade anti-apoptotic molecules in cells induced to undergo apoptosis. The c-IAP1 and XIAP inhibitors of apoptosis were selectively lost in glucocorticoid- or etoposide-treated thymocytes in a proteasome-dependent manner before death. IAPs catalyzed their own ubiquitination in vitro, an activity requiring the RING domain. Overexpressed wild-type c-IAP1, but not a RING domain mutant, was spontaneously ubiquitinated and degraded, and stably expressed XIAP lacking the RING domain was relatively resistant to apoptosis-induced degradation and, correspondingly, more effective at preventing apoptosis than wild-type XIAP. Autoubiquitination and degradation of IAPs may be a key event in the apoptotic program.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Y -- Fang, S -- Jensen, J P -- Weissman, A M -- Ashwell, J D -- New York, N.Y. -- Science. 2000 May 5;288(5467):874-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Immune Cell Biology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10797013" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
*Apoptosis
;
Cells, Cultured
;
Cysteine Endopeptidases/*metabolism
;
Dexamethasone/pharmacology
;
Etoposide/pharmacology
;
Hybridomas
;
Inhibitor of Apoptosis Proteins
;
Ligases/*metabolism
;
Mice
;
Mice, Inbred C57BL
;
Multienzyme Complexes/*metabolism
;
Proteasome Endopeptidase Complex
;
Protein Structure, Tertiary
;
Proteins/chemistry/genetics/*metabolism
;
Recombinant Fusion Proteins/metabolism
;
T-Lymphocytes/cytology/drug effects/*metabolism
;
Thymus Gland/cytology
;
Transfection
;
Ubiquitin-Protein Ligases
;
Ubiquitins/metabolism
;
X-Linked Inhibitor of Apoptosis Protein
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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