| First Author | Chen PJ | Year | 2015 |
| Journal | Nucleic Acids Res | Volume | 43 |
| Issue | 19 | Pages | 9393-404 |
| PubMed ID | 26446990 | Mgi Jnum | J:233868 |
| Mgi Id | MGI:5788236 | Doi | 10.1093/nar/gkv1010 |
| Citation | Chen PJ, et al. (2015) NPGPx modulates CPEB2-controlled HIF-1alpha RNA translation in response to oxidative stress. Nucleic Acids Res 43(19):9393-404 |
| abstractText | Non-selenocysteine-containing phospholipid hydroperoxide glutathione peroxidase (NPGPx or GPx7) is an oxidative stress sensor that modulates the antioxidative activity of its target proteins through intermolecular disulfide bond formation. Given NPGPx's role in protecting cells from oxidative damage, identification of the oxidative stress-induced protein complexes, which forms with key stress factors, may offer novel insight into intracellular reactive oxygen species homeostasis. Here, we show that NPGPx forms a disulfide bond with the translational regulator cytoplasmic polyadenylation element-binding protein 2 (CPEB2) that results in negative regulation of hypoxia-inducible factor 1-alpha (HIF-1alpha) RNA translation. In NPGPx-proficient cells, high oxidative stress that disrupts this bonding compromises the association of CPEB2 with HIF-1alpha RNA, leading to elevated HIF-1alpha RNA translation. NPGPx-deficient cells, in contrast, demonstrate increased HIF-1alpha RNA translation under normoxia with both impaired induction of HIF-1alpha synthesis and blunted HIF-1alpha-programmed transcription following oxidative stress. Together, these results reveal a molecular mechanism for how NPGPx mediates CPEB2-controlled HIF-1alpha RNA translation in a redox-sensitive manner. |
