Document Detail


Beclin 1-independent autophagy induced by a Bcl-XL/Bcl-2 targeting compound, Z18.
MedLine Citation:
PMID:  20818185     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Inhibitors of Bcl-XL/Bcl-2 can induce autophagy by releasing the autophagic protein Beclin 1 from its complexes with these proteins. Here we report a novel compound targeting the BH3 binding groove of Bcl-XL/Bcl-2, Z18, which efficiently induces autophagy-associated cell death in HeLa cells, without apparent apoptosis. Unexpectedly, the inhibition of Beclin 1 and phosphatidylinositol 3-kinase have no obvious effect on Z18-induced autophagy in HeLa cells, implying that it is a non-canonical Beclin 1-independent autophagy. Meanwhile, the accumulation of autophagosomes is positively correlated with Z18-induced cell death and the full flux of autophagy is not necessary.
Authors:
Songhai Tian; Jian Lin; Jian Jun Zhou; Xiaolong Wang; Yanjun Li; Xiaobai Ren; Wenyu Yu; Wu Zhong; Junhai Xiao; Fugeng Sheng; Yingyu Chen; Changwen Jin; Song Li; Zhibing Zheng; Bin Xia
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Autophagy     Volume:  6     ISSN:  1554-8635     ISO Abbreviation:  Autophagy     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-30     Completed Date:  2011-03-02     Revised Date:  2011-06-30    
Medline Journal Info:
Nlm Unique ID:  101265188     Medline TA:  Autophagy     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1032-41     Citation Subset:  IM    
Affiliation:
Beijing Nuclear Magnetic Resonance Center, College of Chemistry and Molecular Engineering, and College of Life Sciences, Peking University; Beijing, China.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis Regulatory Proteins / metabolism
Autophagy / drug effects*
Binding Sites
Hela Cells
Humans
Indoles / chemistry,  pharmacology*,  toxicity
Membrane Proteins / metabolism
Models, Biological
Thiophenes / chemistry,  pharmacology*,  toxicity
bcl-X Protein / antagonists & inhibitors*,  chemistry,  metabolism
Chemical
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/BECN1 protein, human; 0/Indoles; 0/Membrane Proteins; 0/Thiophenes; 0/bcl-X Protein

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