Subcellular localization of Daxx determines its opposing functions in ischemic cell death.
This study examined the role of Daxx in ischemic stress. Upon ischemic stress, nuclear export of Daxx to the cytoplasm was observed in primary myocytes as well as in various cell lines. Daxx silencing using siRNAs was detrimental in tethering PML-nuclear body (PML-NB) constituents together. Overexpression of Daxx (W621A) caused nuclear export of p53 independently of PML and promoted ischemic cell death via activation of JNK. Conversely, overexpression of Daxx (S667A) prevented dissociation of PML-NB constituents and protected cells from ischemic death. Collectively, our results demonstrate that the subcellular localization of Daxx determines its role in ischemic cell death.
Jung
Yong-Sam
YS
Department of Bioscience and Biotechnology, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejeon 305-764, Republic of Korea.
Kim
Hye-Young
HY
Lee
Yong J
YJ
Kim
Eunhee
E
D021581:Active Transport, Cell Nucleus; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D016923:Cell Death / Q000502:physiology*; D002460:Cell Line; D056970:Co-Repressor Proteins; D053200:Fas-Associated Death Domain Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007511:Ischemia / Q000378:metabolism* / Q000473:pathology*; D018832:Molecular Chaperones; D032342:Muscle Cells / Q000378:metabolism / Q000473:pathology; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; C505535:Fadd protein, rat; D053200:Fas-Associated Death Domain Protein; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D011994:Recombinant Proteins