Quinone Reductase 2 Roles in Proteomic Regulation and Response to Treatment with Clinical Drugs
Abstract
Detoxification of quinone compounds is catalyzed by the NQO1 protein in humans. The related NQO2 is distinct from NQO1 as it uses NRH preferentially as a co-substrate to the exclusion of NAD(P)H. It is uncertain if NRH is available in cells for use by NQO2 and raises doubts that quinone detoxification is the adaptive role for NQO2. This study employed cell biology, protein structure and proteomics approaches to identify functions for NQO2 relevant to a cellular context. Several NQO2 interacting clinical drugs were found to have cytotoxic effects dependent upon NQO2 expression. Results from proteomic experiments identified novel roles for NQO2 in regulating lysosome and exosome proteins. Taken together the findings of this thesis are consistent with the hypothesis that NQO2 plays an alternative role in cells. NQO2 is proposed to function as a regulator of various cellular functions by acting as a redox switch rather than a quinone reductase.