The Ubiquitin-like Protein FAT10 Stabilizes eEF1A1 Expression to Promote Tumor Proliferation in a Complex Manner
The Ubiquitin-like Protein FAT10 Stabilizes eEF1A1 Expression to Promote Tumor Proliferation in a Complex Manner
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泛素样蛋白 FAT10 稳定 eEF1A1 表达，以复杂的方式促进肿瘤增殖
DOI：
10.1158/0008-5472.can-15-3118
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发表时间：
2016-08-15
期刊：
影响因子：
11.2
通讯作者：
Shao, Jianghua
中科院分区：
文献类型：
--
作者：
Liu, Xiuxia;Chen, Leifeng;Shao, Jianghua
人HLA-F邻近转录物10 （FAT10）是唯一可以直接靶向底物被蛋白酶体降解的泛素样蛋白，但它也可以通过拮抗泛素化来稳定某些底物的表达，其机制尚未明确。在这项研究中，我们展示了FAT10如何稳定翻译延伸因子eEF1A1，这有助于癌细胞的增殖。过表达FAT10增加eEF1A1的表达，足以促进癌细胞的增殖。机制研究显示，FAT10与泛素（Ub）竞争，分别结合到eEF1A1上相同的赖氨酸上，形成FAT10-eEF1A1或Ub-eEF1A1复合物，因此FAT10过表达降低了Ub-eEF1A1水平，增加了FAT10-eEF1A1水平。总的来说，我们的工作建立了FAT10稳定其底物的新机制，促进了对FAT10生物学功能及其在癌症中的作用的理解。(c) 2016年aacr。
Human HLA-F adjacent transcript 10 (FAT10) is the only ubiquitin-like protein that can directly target substrates for degradation by proteasomes, but it can also stabilize the expression of certain substrates by antagonizing ubiquitination, through mechanisms as yet uncharacterized. In this study, we show how FAT10 stabilizes the translation elongation factor eEF1A1, which contributes to cancer cell proliferation. FAT10 overexpression increased expression of eEF1A1, which was sufficient to promote proliferation of cancer cells. Mechanistic investigations revealed that FAT10 competed with ubiquitin (Ub) for binding to the same lysines on eEF1A1 to form either FAT10-eEF1A1 or Ub-eEF1A1 complexes, respectively, such that FAT10 overexpression decreased Ub-eEF1A1 levels and increased FAT10-eEF1A1 levels. Overall, our work establishes a novel mechanism through which FAT10 stabilizes its substrates, advancing understanding of the biological function of FAT10 and its role in cancer. (C) 2016 AACR.