Document Detail


Gradients of a ubiquitin E3 ligase inhibitor and a caspase inhibitor determine differentiation or death in spermatids.
MedLine Citation:
PMID:  20643358     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Caspases are executioners of apoptosis but also participate in a variety of vital cellular processes. Here, we identified Soti, an inhibitor of the Cullin-3-based E3 ubiquitin ligase complex required for caspase activation during Drosophila spermatid terminal differentiation (individualization). We further provide evidence that the giant inhibitor of apoptosis-like protein dBruce is a target for the Cullin-3-based complex, and that Soti competes with dBruce for binding to Klhl10, the E3 substrate recruitment subunit. We then demonstrate that Soti is expressed in a subcellular gradient within spermatids and in turn promotes proper formation of a similar dBruce gradient. Consequently, caspase activation occurs in an inverse graded fashion, such that the regions of the developing spermatid that are the last to individualize experience the lowest levels of activated caspases. These findings elucidate how the spatial regulation of caspase activation can permit caspase-dependent differentiation while preventing full-blown apoptosis.
Authors:
Yosef Kaplan; Liron Gibbs-Bar; Yossi Kalifa; Yael Feinstein-Rotkopf; Eli Arama
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Developmental cell     Volume:  19     ISSN:  1878-1551     ISO Abbreviation:  Dev. Cell     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-20     Completed Date:  2010-08-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101120028     Medline TA:  Dev Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  160-73     Citation Subset:  IM    
Copyright Information:
(c) 2010 Elsevier Inc. All rights reserved.
Affiliation:
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, 76100, Israel.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / physiology
Caspases / antagonists & inhibitors*
Cell Differentiation / physiology
Cullin Proteins / genetics,  metabolism
Drosophila Proteins / genetics,  metabolism
Drosophila melanogaster / cytology,  genetics,  metabolism
Enzyme Inhibitors / metabolism
Genes, Insect
Male
Models, Biological
Mutation
Saccharomyces cerevisiae / metabolism
Spermatids / cytology*,  metabolism*
Spermatogenesis / genetics,  physiology
Ubiquitin-Protein Ligases / antagonists & inhibitors*
Chemical
Reg. No./Substance:
0/Bruce protein, Drosophila; 0/Cullin Proteins; 0/Drosophila Proteins; 0/Enzyme Inhibitors; 0/gft protein, Drosophila; EC 3.4.22.-/Caspases; EC 6.3.2.19/Ubiquitin-Protein Ligases

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