Inflammatory Mediators Increase SUMOylation of Retinoid X Receptor a in a c-Jun N-Terminal Kinase–Dependent Manner

Retinoid X receptor a [RXRa; nuclear receptor (NR)2B1] is a crucial regulator in the expression of a broad array of hepatic genes under both normal and pathologic conditions. During inflammation, RXRa undergoes rapid post-translational mod-ifications, including c-Jun N-terminal kinase (JNK)-mediated phosphorylation, which correlates with a reduction in RXRa function. A small ubiquitin-like modifier (SUMO) acceptor site was recently described in human RXRa, yet the contributors, regulators, and consequences of SUMO-RXRa are not well understood. Inflammation and other stressors alter nuclear receptor function in liver and induce SUMOylation of several NRs as part of proinflammatory gene regulation, but linkages between these two pathways in liver, or for RXRa directly, remain unexplored. We sought to determine if inflammatio