Ryu Hyunju, Gygi Steven P, Azuma Yoshiaki, Arnaoutov Alexei, Dasso Mary
National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Cell Rep. 2014 Jun 26;7(6):1842-8. doi: 10.1016/j.celrep.2014.05.009. Epub 2014 Jun 5.
SUMOylation is the covalent conjugation of SUMO polypeptides to cellular target proteins. Psmd1 is a subunit of the proteasomal 19S regulatory particle that acts as a docking site for Adrm1, another proteasome subunit that recruits ubiquitinated substrates for proteolysis. Here, we show that the SUMO deconjugating enzyme xSENP1 specifically interacts with Psmd1 and that disruption of xSENP1 targeting delays mitotic exit. Psmd1 becomes SUMOylated through the action of the SUMO E3 enzyme PIASy. We mapped SUMOylation sites within Psmd1 and found that SUMOylation of a critical lysine immediately adjacent to the Adrm1-binding domain regulates the association of Adrm1 with Psmd1. Together, our findings suggest that the interaction of Psmd1 with Adrm1 is controlled by SUMOylation in a manner that may alter proteasome composition and function. These findings demonstrate a mechanism for regulation of ubiquitin-mediated protein degradation by ubiquitin-like proteins of the SUMO family.
小泛素样修饰（SUMO）化是SUMO多肽与细胞靶蛋白的共价结合。Psmd1是蛋白酶体19S调节颗粒的一个亚基，作为Adrm1的对接位点，Adrm1是另一个蛋白酶体亚基，负责募集泛素化底物进行蛋白水解。在此，我们表明SUMO去共轭酶xSENP1与Psmd1特异性相互作用，并且xSENP1靶向的破坏会延迟有丝分裂退出。Psmd1通过SUMO E3酶PIASy的作用而发生SUMO化。我们绘制了Psmd1内的SUMO化位点，发现紧邻Adrm1结合域的一个关键赖氨酸的SUMO化调节Adrm1与Psmd1的结合。总之，我们的研究结果表明，Psmd1与Adrm1的相互作用受SUMO化控制，其方式可能会改变蛋白酶体的组成和功能。这些发现证明了SUMO家族的类泛素蛋白对泛素介导的蛋白质降解的调控机制。
