JNK activation mediates the apoptosis of xCT-deficient cells.
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.
Qiao
Hai-Xuan
HX
Key Laboratory of Molecular and Developmental Biology, Institute of Genetics & Developmental Biology, Chinese Academy of Sciences, Datun Road, Chaoyang District, Beijing, China.
Hao
Chan-Juan
CJ
Li
Yan
Y
He
Xin
X
Chen
Ri-Sheng
RS
Cui
Jie
J
Xu
Zhi-Heng
ZH
Li
Wei
W
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
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