Abstract 834: NRH:quinone oxidoreductase 2 (NQO2) stabilization of C/EBPα against 20S proteasomal degradation leads to protection against radiation-induced myeloproliferative diseases.

Abstract

Abstract NRH:quinone oxidoreductase 2 (NQO2) is a flavoprotein that protects cells against radiation and chemical induced oxidative stress. Disruption of NQO2 gene in mice leads to γ-radiation-induced myeloproliferative diseases. In this report, we found that NQO2 in presence of its cofactor NRH protected C/EBPα against 20S degradation. Coimmunoprecipitation studies showed that 20S proteasome and NQO2 both interact with myeloid differentiation factor C/EBPα. 20S proteasome interaction with C/EBPα led to the degradation of C/EBPα. Deletion and site-directed mutagenesis demonstrated that NQO2 and 20S competed for the same binding region of S(268)GAGAGKAKKSV(279) in C/EBPα. Exposure of mice and HL-60 cells to γ-radiation enhanced the levels of NQO2, which led to increased NQO2 interaction with C/EBPα and decreased 20S interaction with C/EBPα. This resulted in the stabilization of C/EBPα and protection against γ-radiation-induced myeloproliferative diseases. NQO2-/- mice deficient in NQO2 failed to stabilize C/EBPα. This contributed to the development of γ-radiation-induced myeoproliferative disease in NQO2-/- mice. Citation Format: Junkang Xu, Anil Jaiswal. NRH:quinone oxidoreductase 2 (NQO2) stabilization of C/EBPα against 20S proteasomal degradation leads to protection against radiation-induced myeloproliferative diseases. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 834. doi:10.1158/1538-7445.AM2013-834