Yukita Akira, Michiue Tatsuo, Fukui Akimasa, Sakurai Kenji, Yamamoto Hideki, Ihara Motomasa, Kikuchi Akira, Asashima Makoto
Department of Biological Sciences, Graduate School of Sciences, University of Tokyo, 7-8-1, Hongo, Bunkyo-ku, 113-0033, Japan.
Genes Cells. 2004 Aug;9(8):723-36. doi: 10.1111/j.1356-9597.2004.00757.x.
Small ubiqutin-related modifier (SUMO), which is responsible for the ubiquitination-like post-translational modification 'sumoylation', regulates a number of biological processes including, in particular, transcription. The rat protein Axam, which possesses SUMO-specific protease activity, was shown to inhibit the Wnt signalling pathway. Several other components of the pathway are also sumoylated, so the mechanism of this modification has itself been linked to Wnt signalling. However, the functional interactions between SUMO and Wnt signalling are not well understood. This study identified a novel SUMO-specific protease in Xenopus, which was denoted XSENP1. The C-terminus of XSENP1 is highly conserved across the SUMO-specific protease family, and in vitro XSENP1 possesses hydrolase and desumoylation activity. Over-expression of XSENP1 in vivo inhibited dorso-anterior development of Xenopus embryos and suppressed Wnt signalling target gene expression in a manner similar to Axam. Deletion analysis of XSENP1 showed that inhibition of the Wnt signalling pathway requires protease activity. Moreover, XSENP1 inhibits ectopic axis induction by Dvl, beta-catenin and the constitutively active form of beta-catenin, but not by siamois. These results indicate that the dorsal expression of XSENP1 obstructs head development in Xenopus laevis and that this effect may result from inhibition of the canonical Wnt pathway downstream of beta-catenin, but upstream of siamois.
小泛素相关修饰物（SUMO）负责类泛素化的翻译后修饰“类泛素化修饰”，调控许多生物学过程，尤其是转录过程。大鼠蛋白Axam具有SUMO特异性蛋白酶活性，已证明其可抑制Wnt信号通路。该信号通路的其他几个组分也会发生类泛素化修饰，因此这种修饰机制本身与Wnt信号传导相关。然而，SUMO与Wnt信号传导之间的功能相互作用尚未得到充分了解。本研究在非洲爪蟾中鉴定出一种新型SUMO特异性蛋白酶，命名为XSENP1。XSENP1的C末端在SUMO特异性蛋白酶家族中高度保守，并且在体外XSENP1具有水解酶和去类泛素化活性。在体内过表达XSENP1会抑制非洲爪蟾胚胎的背前部发育，并以类似于Axam的方式抑制Wnt信号靶基因的表达。对XSENP进行缺失分析表明，抑制Wnt信号通路需要蛋白酶活性。此外，XSENP1可抑制由Dvl、β-连环蛋白和β-连环蛋白组成型活性形式诱导的异位轴形成，但对siamois诱导的异位轴形成无抑制作用。这些结果表明，XSENP1在背侧的表达会阻碍非洲爪蟾头部的发育，这种作用可能是由于抑制了β-连环蛋白下游但siamois上游的经典Wnt通路所致。
