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Physical interactions and functional coupling between Daxx and sodium hydrogen exchanger 1 in ischemic cell death

Authors
 Yong-SamJung  ;  Hye-Young Kim  ;  Juno Kim  ;  Min-Goo Lee  ;  Jacques Pouysse´gur  ;  Eunhee Kim 
Citation
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.283(2) : 1018-1025, 2008 
Journal Title
 JOURNAL OF BIOLOGICAL CHEMISTRY 
ISSN
 0021-9258 
Issue Date
2008
MeSH
Adult ; Humans ; Lens Implantation, Intraocular/methods* ; Lenses, Intraocular* ; Male ; Marfan Syndrome/complications ; Pupil Disorders/etiology* ; Recurrence ; Sclera/surgery* ; Silicone Elastomers* ; Suture Techniques ; Visual Acuity
Keywords
Adult ; Humans ; Lens Implantation, Intraocular/methods* ; Lenses, Intraocular* ; Male ; Marfan Syndrome/complications ; Pupil Disorders/etiology* ; Recurrence ; Sclera/surgery* ; Silicone Elastomers* ; Suture Techniques ; Visual Acuity
Abstract
Daxx, a death domain-associated protein, is implicated in ischemic cell death. To clarify the mechanism of cell death mediated by Daxx, a yeast two-hybrid assay was performed. Sodium hydrogen exchanger isoform 1 (NHE1) was identified as a Daxx-interacting protein. During ischemic stress, Daxx translocates from the nucleus to the cytoplasm, where it colocalizes with NHE1. Daxx binds to the ezrin/radixin/moesin-interacting domain of NHE1, in competition with ezrin. Consistent with this finding, transfection of the constitutively cytoplasmic mutant, Daxx(W621A), inhibited ezrin-mediated Akt-1 activation. Moreover, transfection of Daxx(W621A), but not the Daxx(S667A) mutant that is confined to the nucleus, accelerated pH(i) recovery from an acid load, indicating that the cytoplasmic protein activates NHE1. Based on the results, we propose that ischemic insult triggers the nucleocytoplasmic translocation of Daxx, following which cytoplasmic Daxx stimulates the NHE1 transporter activity and suppresses activation of the NHE1-ezrin-Akt-1 pathway. Our data support a novel molecular function of Daxx as an upstream regulator of NHE1 in ischemic cell death
Files in This Item:
T200800009.pdf Download
DOI
10.1074/jbc.M707722200
Appears in Collections:
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Eun Hee(김은희)
Kim, Jun O(김준오)
Kim, Hye Young(김혜영)
Lee, Min Goo(이민구) ORCID logo https://orcid.org/0000-0001-7436-012X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/106132
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