Overview of the structure-based non-genomic effects of the nuclear receptor RXR?.

ABSTRACT: The nuclear receptor RXR? (retinoid X receptor-?) is a transcription factor that regulates the expression of multiple genes. Its non-genomic function is largely related to its structure, polymeric forms and modification. Previous research revealed that some non-genomic activity of RXR? occurs via formation of heterodimers with Nur77. RXR?-Nur77 heterodimers translocate from the nucleus to the mitochondria in response to certain apoptotic stimuli and this activity correlates with cell apoptosis. More recent studies revealed a significant role for truncated RXR? (tRXR?), which interacts with the p85? subunit of the PI3K/AKT signaling pathway, leading to enhanced activation of AKT and promoting cell growth in vitro and in animals. We recently reported on a series of NSAID sulindac analogs that can bind to tRXR? through a unique binding mechanism. We also identified one analog, K-80003, which can inhibit cancer cell growth by inducing tRXR? to form a tetramer, thus disrupting p85?-tRXR? interaction. This review analyzes the non-genomic effects of RXR? in normal and tumor cells, and discusses the functional differences based on RXR? protein structure (structure source: the RCSB Protein Data Bank).

SUBMITTER: Chen L 

PROVIDER: S-EPMC6080560 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature