Mutual regulation between OGT and XIAP to control colon cancer cell growth and invasion.
Mutual regulation between OGT and XIAP to control colon cancer cell growth and invasion.
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DOI：
10.1038/s41419-020-02999-5
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发表时间：
2020-09-29
影响因子：
9
通讯作者：
Cho JW
中科院分区：
文献类型：
--
作者：
Seo HG;Kim HB;Yoon JY;Kweon TH;Park YS;Kang J;Jung J;Son S;Yi EC;Lee TH;Yang WH;Cho JW
O-GlcNAc转移酶（OGT）是一种催化核质蛋白O-GlcNAc修饰的酶，在许多类型的癌症中高度表达。然而，调节其在癌细胞中表达的机制尚不清楚。这项研究表明，OGT是E3泛素连接酶X连锁凋亡抑制因子（XIAP）的底物，XIAP在癌症发病机制中起重要作用。虽然LSD 2组蛋白去甲基化酶已经被报道为肺癌细胞中的E3泛素连接酶，但我们鉴定XIAP为结肠癌细胞中的主要E3泛素连接酶。有趣的是，OGT催化XIAP在丝氨酸406处的O-GlcNAc修饰，并且该修饰是XIAP特异性朝向OGT的E3泛素连接酶活性所需的。此外，XIAP的O-GlcNAc化通过促进OGT的蛋白酶体降解来抑制结肠癌细胞的生长和侵袭。因此，我们关于OGT和XIAP的相互调节的研究结果为控制OGT和O-GlcNAc修饰调节的癌症生长和侵袭提供了新的分子机制。
O-GlcNAc transferase (OGT) is an enzyme that catalyzes the O-GlcNAc modification of nucleocytoplasmic proteins and is highly expressed in many types of cancer. However, the mechanism regulating its expression in cancer cells is not well understood. This study shows that OGT is a substrate of the E3 ubiquitin ligase X-linked inhibitor of apoptosis (XIAP) which plays an important role in cancer pathogenesis. Although LSD2 histone demethylase has already been reported as an E3 ubiquitin ligase in lung cancer cells, we identified XIAP as the main E3 ubiquitin ligase in colon cancer cells. Interestingly, OGT catalyzes the O-GlcNAc modification of XIAP at serine 406 and this modification is required for the E3 ubiquitin ligase activity of XIAP toward specifically OGT. Moreover, O-GlcNAcylation of XIAP suppresses colon cancer cell growth and invasion by promoting the proteasomal degradation of OGT. Therefore, our findings regarding the reciprocal regulation of OGT and XIAP provide a novel molecular mechanism for controlling cancer growth and invasion regulated by OGT and O-GlcNAc modification.
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