Document Detail


Non-muscle myosin IIB helps mediate TNF cell death signaling independent of actomyosin contractility (AMC).
MedLine Citation:
PMID:  20564232     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Non-muscle myosin II (NM II) helps mediate survival and apoptosis in response to TNF-alpha (TNF), however, NM II's mechanism of action in these processes is not fully understood. NM II isoforms are involved in a variety of cellular processes and differences in their enzyme kinetics, localization, and activation allow NM II isoforms to have distinct functions within the same cell. The present study focused on isoform specific functions of NM IIA and IIB in mediating TNF induced apoptosis. Results show that siRNA knockdown of NM IIB, but not NM IIA, impaired caspase cleavage and nuclear condensation in response to TNF. NM II's function in promoting cell death signaling appears to be independent of actomyosin contractility (AMC) since treatment of cells with blebbistatin or cytochalasin D failed to inhibit TNF induced caspase cleavage. Immunoprecipitation studies revealed associations of NM IIB with clathrin, FADD, and caspase 8 in response to TNF suggesting a role for NM IIB in TNFR1 endocytosis and the formation of the death inducing signaling complex (DISC). These findings suggest that NM IIB promotes TNF cell death signaling in a manner independent of its force generating property.
Authors:
Patrick G Flynn; David M Helfman
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  110     ISSN:  1097-4644     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-20     Completed Date:  2010-10-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1365-75     Citation Subset:  IM    
Copyright Information:
(c) 2010 Wiley-Liss, Inc.
Affiliation:
Department of Cell Biology and Anatomy Miller School of Medicine, University of Miami, Miami, Florida 33136, USA.
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MeSH Terms
Descriptor/Qualifier:
Actomyosin / metabolism*
Apoptosis / drug effects*
Blotting, Western
Caspase 8 / metabolism
Clathrin / metabolism
Endocytosis / drug effects
Fas-Associated Death Domain Protein / metabolism
Hela Cells
Humans
Immunoprecipitation
Microscopy, Fluorescence
Nonmuscle Myosin Type IIA / genetics,  metabolism
Nonmuscle Myosin Type IIB / genetics,  metabolism*
Protein Binding / drug effects
RNA Interference
Receptors, Tumor Necrosis Factor, Type I / metabolism
Signal Transduction / drug effects
Tumor Necrosis Factor-alpha / pharmacology*
Chemical
Reg. No./Substance:
0/Clathrin; 0/Fadd protein, rat; 0/Fas-Associated Death Domain Protein; 0/Receptors, Tumor Necrosis Factor, Type I; 0/Tumor Necrosis Factor-alpha; 9013-26-7/Actomyosin; EC 3.4.22.-/Caspase 8; EC 3.6.1.-/Nonmuscle Myosin Type IIA; EC 3.6.1.-/Nonmuscle Myosin Type IIB

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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