Abstract
SUMOylation—protein modification by the small ubiquitin-related modifier (SUMO)—affects several cellular processes by modulating the activity, stability, interactions or subcellular localization of a variety of substrates. SUMO modification is involved in most cellular processes required for the maintenance of metabolic homeostasis. Cholesterol is one of the main lipids required to preserve the correct cellular function, contributing to the composition of the plasma membrane and participating in transmembrane receptor signalling. Besides these functions, cholesterol is required for the synthesis of steroid hormones, bile acids, oxysterols and vitamin D. Cholesterol levels need to be tightly regulated: in excess, it is toxic to the cell, and the disruption of its homeostasis is associated with various disorders like atherosclerosis and cardiovascular diseases. This review focuses on the role of SUMO in the regulation of proteins involved in the metabolism of cholesterol.
Highlights
Cholesterol plays essential roles in the cellular organization and takes part in a variety of intracellular mechanisms
We focused on the role that modifications by the small ubiquitin-related modifier (SUMO) exert in proteins involved in cholesterol biosynthesis, uptake, transport and secretion, that is in the regulation of cholesterol homeostasis
This study shows the in vivo function of LRH-1 SUMOylation in cholesterol homeostasis and atherosclerosis
Summary
Cholesterol plays essential roles in the cellular organization and takes part in a variety of intracellular mechanisms. The disruption of cholesterol homeostasis associated with several diseases reveals its importance in human health. Defects in cholesterol biosynthesis cause the Smith–Lemli–Opitz syndrome, and low cholesterol levels are associated with the risk of neuropsychiatric disorders [1]. Excessive cholesterol in the body is associated with cardiovascular diseases, and several studies show that increased serum cholesterol levels are correlated with the risk of developing cancer and with cancer progression (reviewed by [2]). There is limited information regarding other post-translational modifications by members of the ubiquitin-like family of proteins (UbLs). We focused on the role that modifications by the small ubiquitin-related modifier (SUMO) exert in proteins involved in cholesterol biosynthesis, uptake, transport and secretion, that is in the regulation of cholesterol homeostasis
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