Document Detail


TMEM166, a novel transmembrane protein, regulates cell autophagy and apoptosis.
MedLine Citation:
PMID:  17492404     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Programmed cell death can be divided into apoptosis and autophagic cell death. We describe the biological activities of TMEM166 (transmembrane protein 166, also known as FLJ13391), which is a novel lysosome and endoplasmic reticulum-associated membrane protein containing a putative TM domain. Overexpression of TMEM166 markedly inhibited colony formation in HeLa cells. Simultaneously, typical morphological characteristics consistent with autophagy were observed by transmission electron microscopy, including extensive autophagic vacuolization and enclosure of cell organelles by double-membrane structures. Further experiments confirmed that the overexpression of TMEM166 increased the punctate distribution of MDC staining and GFP-LC3 in HeLa cells, as well as the LC3-II/LC3-I proportion. On the other hand, TMEM166-transfected HeLa and 293T cells succumbed to cell death with hallmarks of apoptosis including phosphatidylserine externalization, loss of mitochondrial transmembrane potential, caspase activation and chromatin condensation. Kinetic analysis revealed that the appearance of autophagy-related biochemical parameters preceded the nuclear changes typical of apoptosis in TMEM166-transfected HeLa cells. Suppression of TMEM166 expression by small interference RNA inhibited starvation-induced autophagy in HeLa cells. These findings show for the first time that TMEM166 is a novel regulator involved in both autophagy and apoptosis.
Authors:
Lan Wang; Chuanfei Yu; Yang Lu; Pengfei He; Jinhai Guo; Chenying Zhang; Quansheng Song; Dalong Ma; Taiping Shi; Yingyu Chen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Apoptosis : an international journal on programmed cell death     Volume:  12     ISSN:  1360-8185     ISO Abbreviation:  Apoptosis     Publication Date:  2007 Aug 
Date Detail:
Created Date:  2007-06-25     Completed Date:  2007-11-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9712129     Medline TA:  Apoptosis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1489-502     Citation Subset:  IM    
Affiliation:
Laboratory of Medical Immunology, School of Basic Medical Science, Peking University Health Science Center, Beijing, 100083, PR China.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Apoptosis / genetics*
Autophagy / genetics*
Base Sequence
Cells, Cultured
Cloning, Molecular
Endoplasmic Reticulum / metabolism
Hela Cells
Humans
Lysosomes / metabolism
Membrane Potential, Mitochondrial / genetics
Membrane Proteins / genetics,  metabolism,  physiology*
Molecular Sequence Data
Phylogeny
Tissue Distribution
Transfection
Chemical
Reg. No./Substance:
0/Membrane Proteins; 0/TMEM166 protein, human

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