XSENP1, a novel sumo‐specific protease in Xenopus, inhibits normal head formation by down‐regulation of Wnt/β‐catenin signalling
XSENP1, a novel sumo‐specific protease in Xenopus, inhibits normal head formation by down‐regulation of Wnt/β‐catenin signalling
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DOI：
10.1111/j.1356-9597.2004.00757.x
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发表时间：
2004-08
期刊：
影响因子：
2.1
通讯作者：
Akira Yukita;T. Michiue;A. Fukui;K. Sakurai;Hideki Yamamoto;Motomasa Ihara;A. Kikuchi;M. Asashima
中科院分区：
文献类型：
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作者：
Akira Yukita;T. Michiue;A. Fukui;K. Sakurai;Hideki Yamamoto;Motomasa Ihara;A. Kikuchi;M. Asashima
小泛素相关修饰物（SUMO）负责泛素化样翻译后修饰“SUMO化”，调节许多生物学过程，特别是转录。具有SUMO特异性蛋白酶活性的大鼠蛋白Axam显示出抑制Wnt信号通路。该途径的其他几个组分也被sumoylated，因此这种修饰的机制本身与Wnt信号传导有关。然而，SUMO和Wnt信号传导之间的功能相互作用尚未得到很好的理解。这项研究在非洲爪蟾中鉴定了一种新的SUMO特异性蛋白酶，命名为XSENP 1。XSENP 1的C末端在SUMO特异性蛋白酶家族中高度保守，并且在体外XSENP 1具有水解酶和去小泛素化活性。XSENP 1在体内的过表达抑制了爪蟾胚胎的背前发育，并以类似于Axam的方式抑制了Wnt信号靶基因的表达。XSENP 1的缺失分析表明，Wnt信号通路的抑制需要蛋白酶活性。此外，XSENP 1抑制Dvl、β-连环蛋白和组成型活性形式的β-连环蛋白的异位轴诱导，但不抑制siamois的异位轴诱导。这些结果表明，XSENP 1的背侧表达阻碍了非洲爪蟾的头部发育，这种作用可能是由于抑制了β-连环蛋白下游但在暹罗上游的经典Wnt通路。
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, β‐catenin and the constitutively active form of β‐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 β‐catenin, but upstream of siamois.