Thessa confluence rar12/25/2023 ![]() Although it is appreciated that isomers of retinoic acid activate the retinoic acid receptor ( RAR) and retinoid Xmore » receptor (RXR) family of nuclear receptors to elicit cellular changes, the molecular details of retinoic acid action remain poorly defined in immune processes. Abstract: Oxidative metabolites of vitamin A, in particular all-trans-retinoic acid (at RA), have emerged as key factors in immunity by specifying the localization of immune cells to the gut. • RARα is a key nuclear receptor for retinoid-dependent lymphocyte cell adhesion. • Adhesion occurs through a novel binding site within ADAM disintegrin domains. • Vitamin D derivatives inhibit RAR-prompted lymphocyte adhesion. • RAR activation is sufficient to induced lymphocyte cell adhesion. Highlights: • Transcription and translation are required for retinoid-induced lymphocyte adhesion. Retinoids induce integrin-independent lymphocyte adhesion through RAR-α nuclear receptor activity Taken together, our data suggest that E1A is sequestered to the nucleolus by RaRF through a specific interaction, thereby leaving RAR in the nucleoplasm for transcriptional activation. RaRF-mediated RAR repression was impaired by wild-type E1A, but not by the RaRF binding-defective E1A mutant. ![]() Both the RA-dependent interaction of RAR with RaRF and RAR translocation to the nucleolus were disrupted by E1A. However, RaRF overexpression promoted nucleolar translocation of E1A from the nucleoplasm. ![]() Further fluorescence microscopy indicated that E1A and RaRF were located in the nucleoplasm and nucleolus, respectively. An in vitro glutathione-S-transferase (GST) pull-down assay was used to confirm the direct interaction between E1A and RaRF. The first coiled-coil domain of RaRF was sufficient for this interaction. Based on immunoprecipitation (IP) assays, E1A interacts with RaRF through the conserved region 2 (CR2), which is also responsible for pRb binding. Here, we report how adenovirus E1A stimulates RAR activity by associating with RaRF. Recently, we identified a novel corepressor of RAR called the retinoic acid resistance factor ( RaRF) (manuscript submitted). Transcriptional activity of the retinoic acid receptor ( RAR) is regulated by diverse binding partners, including classical corepressors and coactivators, in response to its ligand retinoic acid ( RA). De-repression of RaRF-mediated RAR repression by adenovirus E1A in the nucleolus.
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