Document Detail


RASSF2 associates with and stabilizes the proapoptotic kinase MST2.
MedLine Citation:
PMID:  19525978     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
RASSF2 is a tumour suppressor that in common with the rest of the RASSF family contains Ras association and SARAH domains. We identified the proapoptotic kinases, MST1 and MST2, as the most significant binding partners of RASSF2, confirmed the interactions at endogenous levels and showed that RASSF2 immunoprecipitates active MST1/2. We then showed that RASSF2 can be phosphorylated by a co-immunoprecipitating kinase that is likely to be MST1/2. Furthermore, we showed that RASSF2 and MST2 do indeed colocalize, but whereas RASSF2 alone is nuclear, the presence of MST1 or MST2 results in colocalization in the cytoplasm. Expression of RASSF2 (stably in MCF7 or transiently in HEK-293) increases MST2 levels and knockdown of RASSF2 in HEK-293 cells reduces MST2 levels, in addition colorectal tumour cell lines and primary tumours with low RASSF2 levels show decreased MST2 protein levels. This is likely to be mediated by RASSF2-dependent protection of MST2 against proteolytic degradation. Our findings suggest that MST2 and RASSF2 form an active complex in vivo, in which RASSF2 is maintained in a phosphorylated state and protects MST2 from degradation and turnover. Thus, we propose that the frequent loss of RASSF2 in tumours results in the destablization of MST2 and thus decreased apoptotic potential.
Authors:
W N Cooper; L B Hesson; D Matallanas; A Dallol; A von Kriegsheim; R Ward; W Kolch; F Latif
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-06-15
Journal Detail:
Title:  Oncogene     Volume:  28     ISSN:  1476-5594     ISO Abbreviation:  Oncogene     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-08-20     Completed Date:  2009-09-11     Revised Date:  2013-03-08    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  2988-98     Citation Subset:  IM    
Affiliation:
Section of Medical and Molecular Genetics, Institute of Biomedical Research, University of Birmingham, Birmingham, UK.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Apoptosis*
COS Cells
Cell Line, Tumor
Cercopithecus aethiops
Cytoplasm / metabolism
Epigenesis, Genetic
Hepatocyte Growth Factor / metabolism
Humans
Molecular Sequence Data
Protein Structure, Tertiary
Protein-Serine-Threonine Kinases / metabolism,  physiology*
Proteomics / methods
Proto-Oncogene Proteins / metabolism
Tumor Suppressor Proteins / metabolism,  physiology*
Grant Support
ID/Acronym/Agency:
A7205//Cancer Research UK; //Cancer Research UK
Chemical
Reg. No./Substance:
0/Proto-Oncogene Proteins; 0/RASSF2 protein, human; 0/Tumor Suppressor Proteins; 0/macrophage stimulating protein; 67256-21-7/Hepatocyte Growth Factor; EC 2.7.1.-/STK3 protein, human; EC 2.7.11.1/Protein-Serine-Threonine Kinases
Comments/Corrections

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


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