Institute of Biochemistry II, Medical School, Goethe University, Frankfurt, Germany.
Institut des Technologies Avancées en sciences du Vivant-UPS and IPBS-CNRS, Toulouse Cedex 1, France.
EMBO Rep. 2018 Nov;19(11). doi: 10.15252/embr.201846117. Epub 2018 Sep 10.
Post-translational modifications by ubiquitin-related SUMO modifiers regulate cellular signaling networks and protein homeostasis. While SUMO1 is mainly conjugated to proteins as a monomer, SUMO2/3 can form polymeric chains. Poly-SUMOylation is best understood in the SUMO-targeted ubiquitin ligase (StUbL) pathway, where chains prime proteins for subsequent ubiquitylation by StUbLs. SUMO chains typically form in response to genotoxic or proteotoxic stress and are preferentially linked via lysine 11 of SUMO2/3. Here, we report that K11 of SUMO2/3 undergoes reversible acetylation with SIRT1 being the K11 deacetylase. In a purified system, acetylation of SUMO2/3 impairs chain formation and restricts chain length. In a cellular context, however, K11 acetyl-mimicking SUMO2 does not affect the StUbL pathway, indicating that in cells non-canonical chains are more prevalent. MS-based SUMO proteomics indeed identified non-canonical chain types under basal and stress conditions. Importantly, mimicking K11 acetylation alters chain architecture by favoring K5- and K35-linked chains, while inhibiting K7 and K21 linkages. These data provide insight into SUMO chain signaling and point to a role of K11 acetylation as a modulator of SUMO2/3 chains.
泛素相关 SUMO 修饰物的翻译后修饰调节细胞信号网络和蛋白质动态平衡。虽然 SUMO1 主要作为单体与蛋白质结合，但 SUMO2/3 可以形成多聚链。多聚 SUMO 化在 SUMO 靶向泛素连接酶 (StUbL) 途径中得到了最好的理解，其中链通过 StUbLs 对随后的泛素化作用将蛋白质引发。SUMO 链通常在遗传毒性或蛋白毒性应激下形成，并且优先通过 SUMO2/3 的赖氨酸 11 连接。在这里，我们报告 SUMO2/3 的 K11 可被 SIRT1 作为 K11 去乙酰化酶可逆乙酰化。在纯化系统中，SUMO2/3 的乙酰化会损害链的形成并限制链长。然而，在细胞环境中，K11 乙酰模拟 SUMO2 不会影响 StUbL 途径，这表明在细胞中非典型链更为普遍。基于 MS 的 SUMO 蛋白质组学确实在基础和应激条件下鉴定了非典型的链类型。重要的是，模拟 K11 乙酰化通过有利于 K5 和 K35 连接的链来改变链结构，同时抑制 K7 和 K21 连接。这些数据提供了对 SUMO 链信号的深入了解，并指出 K11 乙酰化作为 SUMO2/3 链的调节剂的作用。
