| First Author | Zhou J | Year | 2009 |
| Journal | Mol Cell Biol | Volume | 29 |
| Issue | 15 | Pages | 4167-76 |
| PubMed ID | 19451227 | Mgi Jnum | J:151342 |
| Mgi Id | MGI:4353570 | Doi | 10.1128/MCB.01067-08 |
| Citation | Zhou J, et al. (2009) Serine 58 of 14-3-3zeta is a molecular switch regulating ASK1 and oxidant stress-induced cell death. Mol Cell Biol 29(15):4167-76 |
| abstractText | Oxidant stress is a ubiquitous stressor with negative impacts on multiple cell types. ASK1 is a central mediator of oxidant injury, but while mechanisms of its inhibition, such as sequestration by 14-3-3 proteins and thioredoxin, have been identified, mechanisms of activation have remained obscure and the signaling pathways regulating this are not clear. Here, we report that phosphorylation of 14-3-3zeta at serine 58 (S58) is dynamically regulated in the cell and that the phosphorylation status of S58 is a critical factor regulating oxidant stress-induced cell death. Phosphorylation of S58 releases ASK1 from 14-3-3zeta, and ASK1 then activates stress-activated protein kinases, leading to cell death. While several members of the mammalian sterile 20 (Mst) family of kinases can phosphorylate S58 when overexpressed, we identify Ste20/oxidant stress response kinase 1 (SOK-1), an Mst family member known to be activated by oxidant stress, as a central endogenous regulator of S58 phosphorylation and thereby of ASK1-mediated cell death. Our findings identify a novel pathway that regulates ASK1 activation and oxidant stress-induced cell death. |
