Ahn Jang-Won, Lee Yun-Ah, Ahn Jin-Hyun, Choi Cheol Yong
Department of Biological Science, Sungkyunkwan University, Suwon, Republic of Korea.
Biochem Biophys Res Commun. 2009 Jan 30;379(1):160-5. doi: 10.1016/j.bbrc.2008.12.043. Epub 2008 Dec 25.
Groucho is a corepressor that forms a macromolecular complex for its corepressor activity, in which HDAC1 is an essential component for the modulation of chromatin structure and transcriptional repression of target genes. Here, we show that Groucho is covalently conjugated with small ubiquitin-related modifier-1 (SUMO-1) in vitro and in vivo. SUMO conjugations of Groucho occur at four different lysine residues. Substitutions of all these residues abolished sumoylation of Groucho and inhibited its corepressor activity. In addition, Groucho corepressor activity was reduced by inhibition of SUMO-1 conjugation via Ubc9 knockdown through expression of short-hairpin RNA against Ubc9. Furthermore, interactions between Groucho and HDAC1 are enhanced by sumoylation of Groucho, which is mediated by the SUMO-interaction motif of HDAC1. Taken together, these findings indicate that Groucho sumoylation increases its corepressor activity by enhancing the recruitment of HDAC1 to Groucho corepressor complex.
Groucho是一种共抑制因子，其通过形成大分子复合物来发挥共抑制活性，其中HDAC1是调节染色质结构和靶基因转录抑制的重要组成部分。在此，我们表明Groucho在体外和体内均与小泛素相关修饰因子1（SUMO-1）发生共价结合。Groucho的SUMO化修饰发生在四个不同的赖氨酸残基上。所有这些残基的替换均消除了Groucho的SUMO化修饰，并抑制了其共抑制活性。此外，通过表达针对Ubc9的短发夹RNA敲低Ubc9来抑制SUMO-1结合，降低了Groucho的共抑制活性。此外，Groucho的SUMO化修饰增强了Groucho与HDAC1之间的相互作用，这是由HDAC1的SUMO相互作用基序介导的。综上所述，这些发现表明Groucho的SUMO化修饰通过增强HDAC1向Groucho共抑制复合物的募集来提高其共抑制活性。
