Document Detail


MCL-1 is a stress sensor that regulates autophagy in a developmentally regulated manner.
MedLine Citation:
PMID:  21139567     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Apoptosis has an important role during development to regulate cell number. In differentiated cells, however, activation of autophagy has a critical role by enabling cells to remain functional following stress. In this study, we show that the antiapoptotic BCL-2 homologue MCL-1 has a key role in controlling both processes in a developmentally regulated manner. Specifically, MCL-1 degradation is an early event not only following induction of apoptosis, but also under nutrient deprivation conditions where MCL-1 levels regulate activation of autophagy. Furthermore, deletion of MCL-1 in cortical neurons of transgenic mice activates a robust autophagic response. This autophagic response can, however, be converted to apoptosis by either reducing the levels of the autophagy regulator Beclin-1, or by a concomitant activation of BAX. Our results define a pathway whereby MCL-1 has a key role in determining cell fate, by coordinately regulating apoptosis and autophagy.
Authors:
Marc Germain; Angela P Nguyen; J Nicole Le Grand; Nicole Arbour; Jacqueline L Vanderluit; David S Park; Joseph T Opferman; Ruth S Slack
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-12-07
Journal Detail:
Title:  The EMBO journal     Volume:  30     ISSN:  1460-2075     ISO Abbreviation:  EMBO J.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-19     Completed Date:  2011-02-22     Revised Date:  2014-09-19    
Medline Journal Info:
Nlm Unique ID:  8208664     Medline TA:  EMBO J     Country:  England    
Other Details:
Languages:  eng     Pagination:  395-407     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Apoptosis / physiology*
Apoptosis Regulatory Proteins / metabolism
Autophagy / physiology*
Fluorescent Antibody Technique
Humans
Immunoblotting
Immunohistochemistry
Membrane Proteins / metabolism
Mice
Mice, Knockout
Myeloid Cell Leukemia Sequence 1 Protein
Neurons / metabolism*
Proto-Oncogene Proteins c-bcl-2 / genetics,  metabolism*
bcl-2-Associated X Protein / metabolism
Grant Support
ID/Acronym/Agency:
R01 HL102175/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/BECN1 protein, human; 0/Mcl1 protein, mouse; 0/Membrane Proteins; 0/Myeloid Cell Leukemia Sequence 1 Protein; 0/Proto-Oncogene Proteins c-bcl-2; 0/bcl-2-Associated X Protein
Comments/Corrections

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


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