Anti-RBX1 monoclonal antibody, clone FQS7961(C)

Cytosolic inhibitor of Nrf2 (INrf2) is an adaptor protein that mediates ubiquitination/degradation of NF-E2-related factor 2 (Nrf2), a master regulator of cytoprotective gene expression. In this paper, we demonstrate that INrf2 degrades endogenous antiapoptotic B-cell CLL/lymphoma 2 (Bcl-2) protein and controls cellular apoptosis. The DGR domain of INrf2 interacts with the BH2 domain of Bcl-2 and facilitates INrf2:Cul3-Rbx1-mediated ubiquitination of Bcl-2 by the conjugation of ubiquitin molecules to lysine17 of Bcl-2. Further studies showed that INrf2 enhanced etoposide-mediated accumulation of Bax, increased release of cytochrome c from mitochondria, activated caspase-3/7, and enhanced DNA fragmentation and apoptosis. Antioxidants antagonized Bcl-2: INrf2 interaction, led to the release and stabilization of Bcl-2, increased Bcl-2: Bax heterodimers and reduced apoptosis. Moreover, dysfunctional/mutant INrf2 in human lung cancer cells failed to degrade Bcl-2, resulting in decreased etoposide and UV/gamma radiation-mediated DNA fragmentation. These data provide the first evidence of INrf2 control of Bcl-2 and apoptotic cell death, with implications in antioxidant protection, survival of cancer cells containing dysfunctional INrf2, and drug resistance. Cell Death and Differentiation (2011) 18, 439-451; doi:10.1038/cdd.2010.114; published online 24 September 2010

The purpose of this study was to assess the prognostic value of RBX1 in patients with non-small cell lung cancer (NSCLC). Quantitative real-time (RT-PCR) and western blot were used to evaluate the mRNA and protein expression of RBX1 in NSCLC and corresponding non-cancerous tissues. Immunohistochemistry was performed to examine the expression of RBX1 in 192 NSCLC tissue samples. Overall survival was evaluated by the Kaplan-Meier method and analyzed by the log-rank test between different groups. The results showed that the RBX1 expression was significantly higher in NSCLC tissues than the corresponding non-cancerous lung tissues. High RBX1 expression was related to poor tumor differentiation, advanced TNM stage, and lymph node metastasis. Patients with high RBX1 expression had poor overall survival than those with high expression levels, which was consistent with the results of the subgroup analysis. Multivariate analysis showed that high RBX1 expression was an unfavorable prognostic factor for NSCLC patients. Our study indicated that RBX1 might play an important role in the observation of prognosis in NSCLC and could be a valuable marker for predicting the treatment outcome in patients with NSCLC. (C) 2016 Elsevier Ltd. All rights reserved.