SUMO化参与了β-连环蛋白依赖性的Tcf-4激活过程。
Sumoylation is involved in beta-catenin-dependent activation of Tcf-4.
作者信息
Yamamoto Hideki, Ihara Motomasa, Matsuura Yoshiharu, Kikuchi Akira
机构信息
Department of Biochemistry, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
出版信息
EMBO J. 2003 May 1;22(9):2047-59. doi: 10.1093/emboj/cdg204.
Sumoylation is involved in mediating protein-protein interactions, subcellular compartmentalization and protein stability. Our analysis of various Wnt signaling molecules revealed that one of them, Tcf-4, is sumoylated at the endogenous level. At least one sumoylation site, Lys297, of Tcf-4 was identified. The sumoylation of Tcf-4 was enhanced by PIASy, a SUMO E3 enzyme, and inhibited by Axam, a desumoylation enzyme. Although PIASy did not affect the interaction of Tcf-4 with beta-catenin or DNA, Tcf-4, SUMO-1 and PIASy were co-localized in the nucleus and present in a complex in the PML body. PIASy enhanced beta-catenin-dependent transcriptional activity of Tcf-4, whereas Axam inhibited it. Reduction of the protein level of Axam by RNA interference led to an increase in sumoylation of Tcf-4 and activation of Tcf-4. Furthermore, beta-catenin and PIASy activated Tcf-4(K297R), in which Lys297 was changed to arginine, less than wild-type Tcf-4. These results suggest that sumoylation of Tcf-4 is involved in beta-catenin-dependent and Tcf-4-mediated gene expression in the Wnt signaling pathway.
SUMO化参与介导蛋白质-蛋白质相互作用、亚细胞区室化和蛋白质稳定性。我们对各种Wnt信号分子的分析表明，其中之一Tcf-4在内源水平发生SUMO化。鉴定出Tcf-4至少一个SUMO化位点，即赖氨酸297。Tcf-4的SUMO化被SUMO E3酶PIASy增强，并被去SUMO化酶Axam抑制。尽管PIASy不影响Tcf-4与β-连环蛋白或DNA的相互作用，但Tcf-4、SUMO-1和PIASy在细胞核中共定位，并存在于PML小体中的一个复合物中。PIASy增强了Tcf-4的β-连环蛋白依赖性转录活性，而Axam则抑制了它。通过RNA干扰降低Axam的蛋白质水平导致Tcf-4的SUMO化增加和Tcf-4的激活。此外，β-连环蛋白和PIASy对赖氨酸297突变为精氨酸的Tcf-4（K297R）的激活作用小于野生型Tcf-4。这些结果表明，Tcf-4的SUMO化参与Wnt信号通路中β-连环蛋白依赖性和Tcf-4介导的基因表达。
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