| First Author | Xu J | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 50 | Pages | 41608-18 |
| PubMed ID | 23086932 | Mgi Jnum | J:193416 |
| Mgi Id | MGI:5468386 | Doi | 10.1074/jbc.M112.387738 |
| Citation | Xu J, et al. (2012) NAD(P)H:quinone oxidoreductase 1 (NQO1) competes with 20S proteasome for binding with C/EBPalpha leading to its stabilization and protection against radiation-induced myeloproliferative disease. J Biol Chem 287(50):41608-18 |
| abstractText | NAD(P)H:quinone oxidoreductase 1 (NQO1) is a flavoprotein that protects cells against radiation and chemical-induced oxidative stress. Disruption of NQO1 gene in mice leads to increased susceptibility to myeloproliferative disease. In this report, we demonstrate that NQO1 controls the stability of myeloid differentiation factor C/EBPalpha against 20S proteasomal degradation during radiation exposure stress. Co-immunoprecipitation studies showed that NQO1, C/EBPalpha, and 20S all interacted with each other. C/EBPalpha interaction with 20S led to the degradation of C/EBPalpha. NQO1 in presence of its cofactor NADH protected C/EBPalpha against 20S degradation. Deletion and site-directed mutagenesis demonstrated that NQO1 and 20S competed for the same binding region (268)SGAGAGKAKKSV(279) in C/EBPalpha. Mutagenesis studies also revealed that NQO1Y127/Y129 required for NADH binding is essential for NQO1 stabilization of C/EBPalpha. Exposure of mice and HL-60 cells to 3 Grays of gamma-radiation led to increased NQO1 that stabilized C/EBPalpha against 20S proteasomal degradation. This mechanism of NQO1 regulation of C/EBPalpha may provide protection to bone marrow against adverse effects of radiation exposure. The studies have significance for human individuals carrying hetero- or homozygous NQO1P187S mutation and are deficient or lack NQO1 protein. |
