title: Transmembrane Protein 214 (TMEM214) mediates endoplasmic reticulum stress-induced caspase 4 enzyme activation and apoptosis.
abstract: Endoplasmic reticulum (ER) stress caused by excessive aggregation of misfolded proteins induces apoptosis. Although ER stress-induced apoptosis has been implicated in many diseases, the detailed mechanisms are not well understood. Here, we identified human transmembrane protein 214 (TMEM214) as a critical mediator of ER stress-induced apoptosis. Overexpression of TMEM214 induced apoptosis, whereas knockdown of TMEM214 inhibited ER stress-induced apoptosis. TMEM214 was localized on the outer membrane of the ER and constitutively associated with procaspase 4, which was also critical for ER stress-induced apoptosis. TMEM214-induced apoptosis was abolished by a dominant negative mutant of procaspase 4, whereas caspase 4-induced apoptosis was inhibited by knockdown of TMEM214. Furthermore, knockdown of TMEM214 inhibited the activation and cleavage of procaspase 4 by impairing its recruitment to the ER. Our findings suggest that TMEM214 is essential for ER stress-induced apoptosis by acting as an anchor for recruitment of procaspase 4 to the ER and its subsequent activation.
authors: College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors: Chao
authors: C
authors: Li
authors: Jin
authors: J
authors: Wei
authors: Ying
authors: Y
authors: Li
authors: Xiao
authors: X
authors: He
authors: Qian
authors: Q
authors: Zhou
authors: Jie
authors: J
authors: Yan
authors: Jing
authors: J
authors: Zhang
authors: Ying
authors: Y
authors: Liu
authors: Yu
authors: Y
authors: Liu
authors: Hong-Bing
authors: HB
authors: Shu
mesh_terms: D017209:Apoptosis; D053179:Caspase 7 / Q000378:metabolism; D053471:Caspases, Initiator / Q000378:metabolism*; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000201:enzymology; D059865:Endoplasmic Reticulum Stress; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D007425:Intracellular Membranes / Q000201:enzymology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D010449:Peptide Mapping; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D034622:RNA Interference
chemical_list: D004792:Enzyme Precursors; D008565:Membrane Proteins; C582960:transmembrane protein 214, human; C093516:CASP4 protein, human; C505520:CASP7 protein, human; D053179:Caspase 7; D053471:Caspases, Initiator
keywords: Apoptosis; Caspase; Caspase 4; Cell Signaling; ER Stress; TMEM214; Unfolded Protein Response
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