Hotz Paul W, Müller Stefan, Mendler Luca
Institute of Biochemistry II, Gustav Embden Zentrum, Faculty of Medicine, Goethe University Frankfurt, Frankfurt, Germany.
Front Mol Biosci. 2021 Nov 19;8:786136. doi: 10.3389/fmolb.2021.786136. eCollection 2021.
SUMOylation is a transient posttranslational modification with small-ubiquitin like modifiers (SUMO1, SUMO2 and SUMO3) covalently attached to their target-proteins via a multi-step enzymatic cascade. SUMOylation modifies protein-protein interactions, enzymatic-activity or chromatin binding in a multitude of key cellular processes, acting as a highly dynamic molecular switch. To guarantee the rapid kinetics, SUMO target-proteins are kept in a tightly controlled equilibrium of SUMOylation and deSUMOylation. DeSUMOylation is maintained by the SUMO-specific proteases, predominantly of the SENP family. SENP1 and SENP2 represent family members tuning SUMOylation status of all three SUMO isoforms, while SENP3 and SENP5 are dedicated to detach mainly SUMO2/3 from its substrates. SENP6 and SENP7 cleave polySUMO2/3 chains thereby countering the SUMO-targeted-Ubiquitin-Ligase (StUbL) pathway. Several biochemical studies pinpoint towards the SENPs as critical enzymes to control balanced SUMOylation/deSUMOylation in cardiovascular health and disease. This study aims to review the current knowledge about the SUMO-specific proteases in the heart and provides an integrated view of cardiac functions of the deSUMOylating enzymes under physiological and pathological conditions.
SUMO化是一种瞬时的翻译后修饰，小泛素样修饰物（SUMO1、SUMO2和SUMO3）通过多步酶促级联反应共价连接到其靶蛋白上。SUMO化在许多关键细胞过程中修饰蛋白质-蛋白质相互作用、酶活性或染色质结合，充当高度动态的分子开关。为确保快速动力学，SUMO靶蛋白在SUMO化和去SUMO化的严格控制平衡中保持。去SUMO化由SUMO特异性蛋白酶维持，主要是SENP家族。SENP1和SENP2是调节所有三种SUMO亚型SUMO化状态的家族成员，而SENP3和SENP5主要负责从其底物上分离SUMO2/3。SENP6和SENP7切割多聚SUMO2/3链，从而对抗SUMO靶向泛素连接酶（StUbL）途径。多项生化研究指出，SENP是控制心血管健康和疾病中SUMO化/去SUMO化平衡的关键酶。本研究旨在综述目前关于心脏中SUMO特异性蛋白酶的知识，并提供去SUMO化酶在生理和病理条件下心脏功能的综合观点。
