title: JNK activation mediates the apoptosis of xCT-deficient cells.
abstract: System X(c)(-) is an anionic amino acid transport system highly specific for cystine and glutamate. The underlying mechanism of cell death of cultured cells from the subtle gray (sut) mouse which contains an xCT null mutation remains elucidated. Our results show that the death of sut cells is likely caused by apoptosis mediated by c-Jun N-terminal kinase (JNK). The JNK activation triggers both a caspase-dependent (caspases-9 and -3) and an ER stress-mediated (eIF2 and CHOP) pathway to induce apoptosis. These findings suggest the possible pathways involved in the cell death of xCT-deficient cells.
authors.affiliation: Key Laboratory of Molecular and Developmental Biology, Institute of Genetics & Developmental Biology, Chinese Academy of Sciences, Datun Road, Chaoyang District, Beijing, China.
authors.forename: Hai-Xuan
authors.initials: HX
authors.lastname: Qiao
authors.forename: Chan-Juan
authors.initials: CJ
authors.lastname: Hao
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: He
authors.forename: Ri-Sheng
authors.initials: RS
authors.lastname: Chen
authors.forename: Jie
authors.initials: J
authors.lastname: Cui
authors.forename: Zhi-Heng
authors.initials: ZH
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Li
mesh_terms: D027182:Amino Acid Transport System y+ / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008544:Melanocytes / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D051742:Transcription Factor CHOP / Q000378:metabolism
chemical_list: D027182:Amino Acid Transport System y+; C497250:Ddit3 protein, mouse; D015852:Eukaryotic Initiation Factor-2; C492255:Slc7a11 protein, mouse; D051742:Transcription Factor CHOP; D048031:JNK Mitogen-Activated Protein Kinases; D053148:Caspase 3; D053453:Caspase 9