Positive regulation of apoptosis signal-regulating kinase 1 signaling by ZPR9 protein, a zinc finger protein
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- Title
- Positive regulation of apoptosis signal-regulating kinase 1 signaling by ZPR9 protein, a zinc finger protein
- Author(s)
- H A Seong; Haiyoung Jung; R Manoharan; H Ha
- Bibliographic Citation
- Journal of Biological Chemistry, vol. 286, no. 36, pp. 31123-31135
- Publication Year
- 2011
- Abstract
- A zinc finger protein, ZPR9, has been identified as a physiological substrate of murine protein serine/threonine kinase 38 (MPK38), which is involved in various cellular responses, including the cell cycle, apoptosis, embryonic development, and oncogenesis. Here, ZPR9 was found to physically interact with apoptosis signal-regulating kinase 1 (ASK1) through a disulfide linkage involving Cys 1351 and Cys 1360 of ASK1 and Cys 305 and Cys 308 of ZPR9. ASK1 directly phosphorylated ZPR9 at Ser 314and Thr 318, suggesting that ZPR9 can act as an ASK1 substrate. Ectopic expression of wild-type ZPR9, but not an S314A/T318A mutant, stimulated ASK1 kinase activity and positively regulated ASK1-mediated signaling to both JNK and p38 kinases by destabilizing complex formation between ASK1 and its negative regulators, Trx and 14-3-3, or by increasing complex formation between ASK1 and its substrate MKK3. ZPR9 functionally stimulated ASK1-induced AP-1 transcriptional activity as well as H 2O 2-mediated apoptosis in a phosphorylation-dependent manner. ASK1-mediated phosphorylation of ZPR9 at Ser 314 and Thr 318 was also responsible for ZPR9-induced apoptosis. Moreover, ZPR9 inhibited PDK1-mediated signaling through ASK1 activation. These results suggest that ZPR9 functions as a novel positive regulator of ASK1.
- ISSN
- 0021-9258
- Publisher
- Amer Soc Biochemistry Molecular Biology Inc
- DOI
- http://dx.doi.org/10.1074/jbc.M111.248674
- Type
- Article
- Appears in Collections:
- Aging Convergence Research Center > 1. Journal Articles
- Files in This Item:
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