图1. METTL3-METTL14复合物PROTAC作用示意图 在这项研究中,研究人员尝试开发一种有效的治疗工具,可以破坏METTL3和/或METTL14的稳定性,研究人员以METTL3抑制剂UZH2作为METTL3结合配体,设计并合成了一系列靶向METTL3 PROTACs分子,然后,他们运用Western Bolt研究了...
这些发现表明METTL3-METTL14复合物是癌症治疗,特别是急性髓系白血病(AML)治疗的非常有吸引力的靶点。 2024年1月8日,中国科学院上海药物研究所徐石林团队在 Cell 子刊 Cell Chemical Biology 上发表了题为:Discovery of a PROTAC degrader for METTL3-METTL14 complex 的研究论文。 该研究开...
靶向METTL3-METTL14复合物的PROTAC N 6-甲基腺苷(m6A)甲基化是最丰富的RNA修饰类型,主要由METTL3-METTL14甲基转移酶复合物(MTC)催化。该复合物包含核心催化蛋白METTL3和METTL14,以及多个调节蛋白,包括WTAP、VIRMA、HAKAI、ZC3H13和RBM15等。METTL3是唯一的催化组分,而METTL14主要维护复合物的完整性并促进底物RNA的...
1. Selberg S, Blokhina D, Aatonen M, Koivisto P, Siltanen A, Mervaala E, et al. Discovery of small molecules that activate RNA methylation through cooperative binding to the METTL3-14-WTAP complex active site.Cell ...
Discovery of small molecules that activate RNA methylation through cooperative binding to the METTL3-14-WTAP complex active site. Cell Rep. 2019;26(13):3762–71.2.. Bedi RK, Huang D, Eberle SA, Wiedmer L, Caflisch A, Sledz P. Small-molecule inhibitors of METTL3, the major human ...
METTL3/14是m6A功能调节相关的重要催化酶,目前大部分METTL3/14的功能研究集中在m6A修饰与疾病的关联上,对于修饰酶本身的功能的研究相对很少。m6A甲基化修饰被证明是一个动态可逆的过程,包括甲基化转移酶、去甲基化酶和甲基化阅读蛋白等共同参与(图2.6)。其中甲基化转移酶包括METTL3/14、WTAP和KIAA1429等,主要作用就...
N6-methyladenosine (m6A) is a common modification of mRNA that is catalyzed by the Mettl3–Mettl14 methyltransferase complex1, with WTAP as its regulatory subunit2. The physiological importance of m6A has been evidenced by its pivotal roles in tissue development and differentiation3,4,5,6,7,8,...
N6-methyladenosine (m6A) modification, catalyzed by methyltransferase complexes (MTCs), plays many roles in multifaceted biological activities. As the most important subunit of MTCs, the METTL3-METTL14 complex is reported to be the initial factor that ca
The N 6-methyladenosine (m6A) epitranscriptomic modification controls post-transcriptional gene expression but the mechanism by which the m6A methyltransferase complex METTL3/METTL14/WTAP is recruited to specific loci remains to be fully characterized. We explored whether the m6A epitranscriptome could ...
METTL3, METTL14 and WTAP localization in several AML cell lines, and in all of them we detected METTL3 mislocalization in the cytoplasm while the other compo- nents of the m6A methylation complex were pre- dominantly localized in the nuclear fraction (Fig. 2a). Therein, in view of these...