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lrh1 2017-05-19T09:40:28+00:00

LRH-1 in atherosclerosis

Liver receptor homolog 1 (LRH-1) is a nuclear receptor that is highly expressed in enterohepatic tissues and different metabolic processes, including lipid metabolism and hepatic glucose sensing (Stein, 2015b). In a study that was carried out in the lab of Kristina Schoonjans at the EPFL in Lausanne, we showed that atherosclerosis-prone mice carrying a mutation that abolishes the SUMOylation of the nuclear receptor are significantly protected from atherosclerosis development (Stein, 2014). The mechanism underlying this atheroprotection involves a local increase of reverse cholesterol transport in the liver and is secondary to a compromised interaction of the non-SUMOylatable form of LRH-1 with the co-repressor PROX1. This study highlights that a single posttranslational modification of a specific residue of a transcriptional regulator is sufficient to modulate the function of the protein and the corresponding cellular and metabolic processes, which consequently can affect the development of a complex chronic disease, such as atherosclerosis (Stein, 2014).

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