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Daxx is a key downstream component of receptor interacting protein kinase 3 mediating retinal ischemic cell death
Yun-Suk Lee1, Yogesh Dayma, Min-Young Park
1College of Biological Sciences and Biotechnology, Chungnam National University, Daejeon 305-764, Republic of Korea.
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.
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