title: Daxx is a key downstream component of receptor interacting protein kinase 3 mediating retinal ischemic cell death.
abstract: Receptor-interacting protein 3 (RIP3) has been implicated in ischemic necrosis of retinal cells. An in silico analysis followed by experimental validation identified death associated protein (Daxx) as a novel substrate of RIP3. In vitro binding studies revealed that RIP3 binds to the serine/proline/threonine-rich domain (amino acid 625-740) of Daxx. Upon ischemic insult, RIP3 phosphorylated Daxx at Ser-668 in the retinal ganglion cells, triggering nuclear export of Daxx. Depletion of RIP3 significantly inhibited nuclear export of Daxx and attenuated cell death to a great extent. Collectively, the findings of this study demonstrate that phosphorylation of Daxx by RIP3 comprises an important part of ischemic necrosis in rat retinal ganglion cells.
authors.affiliation: College of Biological Sciences and Biotechnology, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Yun-Suk
authors.initials: YS
authors.lastname: Lee
authors.forename: Yogesh
authors.initials: Y
authors.lastname: Dayma
authors.forename: Min-Young
authors.initials: MY
authors.lastname: Park
authors.forename: Kyung Il
authors.initials: KI
authors.lastname: Kim
authors.forename: Sung-Eun
authors.initials: SE
authors.lastname: Yoo
authors.forename: Eunhee
authors.initials: E
authors.lastname: Kim
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D056970:Co-Repressor Proteins; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D007511:Ischemia / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D018832:Molecular Chaperones; D009336:Necrosis; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D021381:Protein Transport; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000378:metabolism* / Q000473:pathology*; D012694:Serine
chemical_list: D002352:Carrier Proteins; D056970:Co-Repressor Proteins; C491473:Daxx protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D012694:Serine; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C485615:Ripk3 protein, mouse