Role of WTAP in Cancer: From Mechanisms to the Therapeutic Potential.

Role of WTAP in Cancer: From Mechanisms to the Therapeutic Potential.
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DOI:
10.3390/biom12091224
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发表时间:
2022-09-02
期刊:
影响因子:
5.5
通讯作者:
--
中科院分区:
生物学2区
文献类型:
--
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肾母细胞瘤1相关蛋白(WTAP)是N6-甲基腺苷(m6 A)RNA甲基化修饰所必需的,其调节生物学过程,如RNA剪接、细胞增殖、细胞周期和胚胎发育。m6 A是真核生物中mRNA修饰的主要形式。WTAP通过与细胞核中的甲基转移酶样3(Methyltransferase-like 3,简称M3)结合形成M3-M14(M14)-WTAP(MMW)复合物(M3-M14)-M14复合物,M14复合物是M3-M14复合物的核心成分,并定位于细胞核斑片,从而发挥m6 A修饰作用。研究表明,WTAP在各种癌症中起着关键作用,既依赖于也不依赖于其在甲基转移酶的m6 A修饰中的作用。本文就WTAP的结构特征、WTAP调节生物学功能的机制以及其在多种癌症中的作用的分子机制作一综述。通过总结WTAP的最新研究,我们期望为肿瘤学研究提供新的方向和见解,并发现癌症治疗的新靶点。
Wilms’ tumor 1-associating protein (WTAP) is required for N6-methyladenosine (m6A) RNA methylation modifications, which regulate biological processes such as RNA splicing, cell proliferation, cell cycle, and embryonic development. m6A is the predominant form of mRNA modification in eukaryotes. WTAP exerts m6A modification by binding to methyltransferase-like 3 (METTL3) in the nucleus to form the METTL3-methyltransferase-like 14 (METTL14)-WTAP (MMW) complex, a core component of the methyltransferase complex (MTC), and localizing to the nuclear patches. Studies have demonstrated that WTAP plays a critical role in various cancers, both dependent and independent of its role in m6A modification of methyltransferases. Here, we describe the recent findings on the structural features of WTAP, the mechanisms by which WTAP regulates the biological functions, and the molecular mechanisms of its functions in various cancers. By summarizing the latest WTAP research, we expect to provide new directions and insights for oncology research and discover new targets for cancer treatment.
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