Desterro J M, Rodriguez M S, Hay R T
School of Biomedical Science, University of St. Andrews, Fife, United Kingdom.
Mol Cell. 1998 Aug;2(2):233-9. doi: 10.1016/s1097-2765(00)80133-1.
Activation of NF-kappaB is achieved by ubiquitination and proteasome-mediated degradation of IkappaBalpha. We have detected modified IkappaBalpha, conjugated to the small ubiquitin-like protein SUMO-1, which is resistant to signal-induced degradation. In the presence of an E1 SUMO-1-activating enzyme, Ubch9 conjugated SUMO-1 to IkappaBalpha primarily on K21, which is also utilized for ubiquitin modification. Thus, SUMO-1-modified IkappaBalpha cannot be ubiquitinated and is resistant to proteasome-mediated degradation. As a result, overexpression of SUMO-1 inhibits signal-induced activation of NF-kappaB-dependent transcription. Unlike ubiquitin modification, which requires phosphorylation of S32 and S36, SUMO-1 modification of IkappaBalpha is inhibited by phosphorylation. Thus, while ubiquitination targets proteins for rapid degradation, SUMO-1 modification acts antagonistically to generate proteins resistant to degradation.
核因子-κB（NF-κB）的激活是通过IκBα的泛素化和蛋白酶体介导的降解来实现的。我们检测到与小泛素样蛋白SUMO-1偶联的修饰型IκBα，其对信号诱导的降解具有抗性。在E1 SUMO-1激活酶存在的情况下，Ubch9主要在K21位点将SUMO-1偶联到IκBα上，该位点也用于泛素修饰。因此，SUMO-1修饰的IκBα不能被泛素化，并且对蛋白酶体介导的降解具有抗性。结果，SUMO-1的过表达抑制了信号诱导的NF-κB依赖性转录的激活。与需要S32和S36磷酸化的泛素修饰不同，IκBα的SUMO-1修饰受到磷酸化的抑制。因此，虽然泛素化靶向蛋白质进行快速降解，但SUMO-1修饰起拮抗作用以产生抗降解的蛋白质。
