Document Detail


Differential cleavage of Mst1 by caspase-7/-3 is responsible for TRAIL-induced activation of the MAPK superfamily.
MedLine Citation:
PMID:  18276109     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to induce apoptosis through caspase activation in a number of cancer cell lines while displaying minimal or no toxicity on normal cells, suggesting that this protein may hold potential for development as a new cancer therapeutic agent. Moreover, TRAIL can activate mitogen-activated protein kinases (MAPKs) in addition to caspases. However, it has not been clearly understood how MAPKs are activated by TRAIL and the biological significance of their activation. Here we show that TRAIL-induced MAPKs activation is dependent on caspase activation and that mammalian sterile 20-like kinase 1 (Mst1) functions as a mediator between caspase activation and MAPKs activation. Activation of MAPKs (JNK, p38, ERK) is differentially regulated by cleavage size (40 kDa and 36 kDa) of Mst1, which is controlled by caspase-7 and -3.
Authors:
Jae J Song; Yong J Lee
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2008-01-11
Journal Detail:
Title:  Cellular signalling     Volume:  20     ISSN:  0898-6568     ISO Abbreviation:  Cell. Signal.     Publication Date:  2008 May 
Date Detail:
Created Date:  2008-03-07     Completed Date:  2008-05-23     Revised Date:  2013-02-13    
Medline Journal Info:
Nlm Unique ID:  8904683     Medline TA:  Cell Signal     Country:  England    
Other Details:
Languages:  eng     Pagination:  892-906     Citation Subset:  IM    
Affiliation:
Department of Surgery and Pharmacology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
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MeSH Terms
Descriptor/Qualifier:
Base Sequence
Caspase 3 / genetics,  metabolism*
Caspase 7 / genetics,  metabolism*
Cell Line, Tumor
DNA Primers / genetics
Female
Hepatocyte Growth Factor / antagonists & inhibitors,  genetics,  metabolism*
Humans
MAP Kinase Signaling System / drug effects*,  physiology
Male
Mutagenesis, Site-Directed
Proto-Oncogene Proteins / antagonists & inhibitors,  genetics,  metabolism*
RNA, Small Interfering / genetics
Reactive Oxygen Species / metabolism
Recombinant Proteins / genetics,  metabolism,  pharmacology
Sequence Deletion
TNF-Related Apoptosis-Inducing Ligand / genetics,  metabolism,  pharmacology*
Transfection
Grant Support
ID/Acronym/Agency:
CA121395/CA/NCI NIH HHS; CA95191/CA/NCI NIH HHS; CA96989/CA/NCI NIH HHS; R01 CA095191/CA/NCI NIH HHS; R01 CA095191-01A2/CA/NCI NIH HHS; R01 CA096989/CA/NCI NIH HHS; R01 CA096989-01A2/CA/NCI NIH HHS; R03 CA121395/CA/NCI NIH HHS; R03 CA121395-01/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/DNA Primers; 0/Proto-Oncogene Proteins; 0/RNA, Small Interfering; 0/Reactive Oxygen Species; 0/Recombinant Proteins; 0/TNF-Related Apoptosis-Inducing Ligand; 0/TNFSF10 protein, human; 0/macrophage stimulating protein; 67256-21-7/Hepatocyte Growth Factor; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/CASP7 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 7
Comments/Corrections

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