The androgen receptor (AR) plays an essential role in the development of prostate cancer and androgen deprivation therapy is used as a first-line treatment for prostate cancer. However, under androgen deprivation therapy, castration-resistant prostate cancer inevitably arises, suggesting that the interacting transcriptional coregulators of AR are promising targets for developing novel therapeutics. In this study, we utilized novel proteomic techniques to evaluate the AR interactome, including biochemically labile binding proteins, which might go undetected by conventional purification methods. Using rapid immunoprecipitation mass spectrometry of endogenous proteins, we identified enhanced at puberty 1 (EAP1) as a novel AR coregulator, whereas its interaction with AR could not be detected under standard biochemical conditions. EAP1 enhanced the transcriptional activity of AR via the E3 ubiquitin ligase activity and its ubiquitination substrate proteins included AR and HDAC1. Furthermore, in prostate cancer specimens, EAP1 expression was significantly correlated with AR expression as well as a poor prognosis of prostate cancer. Together, these results suggest that EAP1 is a novel AR coregulator that promotes AR activity and potentially plays a role in prostate cancer progression.
Melinjo (Gnetum gnemon L.) is a fruit native to Indonesia and is considered as a healthy food. Melinjo resveratrol (MjR) is a resveratrol derivative extracted from the melinjo seed. Interestingly, recent literatures have documented that MjR exhibits the angiotensin converting enzyme inhibitory activity. Hence, we hypothesized that MjR exhibits beneficial effects in the chronic kidney disease. In order to test our hypothesis, MjR was administered in the rat remnant kidney (RK) model. Rats were divided into three groups: sham operated rats (SHAM, n = 4), untreated remnant kidney rats (RK, n = 5), RK rats treated with MjR 300 mg/kg/day (RK + MjR, n = 5). The rats were sacrificed at twelve weeks.
Hepatocyte nuclear factor 4α (HNF4α) has an essential role in controlling the expression of variety of genes involved in key metabolic pathways including gluconeogenesis in the liver. Though mechanistic and physiological significance of proliferator-activated receptor-gamma co-activator-1α (PGC-1α) for HNF4α-mediated transcriptional activation models for gluconeogenic genes is well characterized, transcriptional repression of HNF4α for those genes still remains to be examined. In this study, we applied novel proteomic techniques to evaluate the HNF4α interactome including biochemically labile binding proteins. From the experiment, we identified interferon regulatory factor 2 binding protein 2 (IRF2BP2) as a novel HNF4α corepressor, with which its interaction could not be detected by conventional immunoprecipitation. IRF2BP2 repressed transcriptional activity of HNF4α dependent on its E3 ubiquitin ligase activity. Deficiency of IRF2BP2 gene in HepG2 cells induced gluconeogenic genes comparable to the forskolin-treated wild type HepG2 cells. Together, these results suggest the role of IRF2BP2 as a novel class of nuclear receptor coregulator.
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