Targeting truncated RXRα for cancer therapy

Abstract

Retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a wellestablished drug target, representing one of the most important targets for pharmacologic interventions and therapeutic applications for cancer. However, how RXRα regulates cancer cell growth and how RXRα modulators suppress tumorigenesis are poorly understood. Altered expression and aberrant function of RXRα are implicated in the development of cancer. Previously, several studies had demonstrated the presence of N-terminally truncated RXRα (tRXRα) proteins resulted from limited proteolysis of RXRα in tumor cells. Recently, we discovered that overexpression of tRXRα can promote tumor growth by interacting with tumor necrosis factor-alpha-induced phosphoinositide 3-kinase and NF-κB signal transduction pathways. We also identified nonsteroidal anti-inflammatory drug Sulindac and analogs as effective inhibitors of tRXRα activities via a unique binding mechanism. This review discusses the emerging roles of tRXRα and modulators in the regulation of cancer cell survival and death as well as inflammation and our recent understanding of tRXRα regulation by targeting the alternate binding sites on its surface.

Rapid LC‐MRM‐MS assay for simultaneous quantification of choline, betaine, trimethylamine, trimethylamine N‐oxide, and creatinine in human plasma and urine

“…Various methods have been established for the measurement of choline and its closely related metabolites in biological samples. Traditionally, choline and betaine were measured either separately or simultaneously by radioenzymatic assays [15,16], LC with an electrochemical detection [17][18][19], and GC-MS [20,21]. Previous methods for TMA and TMAO analysis include GC with a flame ionization detector [22], GC with a nitrogen-phosphorus detector [23], GC-MS [24][25][26][27], fast atom bombardment MS [28], and flow injection ESI MS [29].…”

Formation of Alkanethiol Supported Hybrid Membranes Revisited

“…It has been reported before that FRET to the gold plasmons can quench fluorescence signal, [27] that is, however, more likely to happen with the laser excitation than with the broad emission www.advancedsciencenews.com www.biotechnology-journal.com band of the UV lamp, as the latter directly excites the gold plasmons as well. [53] To assess whether the residual liposomes are connected to an underlying continuous membrane, FRAP measurements were also performed on these liposomes as in a previous work. [13] No fluorescence recovery was observed after 6 min ( Figure S5, Supporting Information) hence the bleached vesicles were isolated from any mobile lipid phase.…”

Comparative proteomic analysis of oil palm leaves infected with Ganoderma boninense revealed changes in proteins involved in photosynthesis, carbohydrate metabolism, and immunity and defense

“…The FC-binding activity increases upon the pathogen attack, suggesting that 14-3-3s are involved in response to the fungus probably through activating the proton pump to stimulate the response. Caffeic acid/5-hydroxyferulic acid O-methyltransferase and ascorbate peroxidase implicated in plant defense or oxidative stress are identified to interact with 14-3-3s by yeast two-hybrid screening in Arabidopsis [45,46].…”