DPY30 acts as an ASH2L-specific stabilizer to stimulate the enzyme activity of MLL family methyltransferases on different substrates.
DPY30 acts as an ASH2L-specific stabilizer to stimulate the enzyme activity of MLL family methyltransferases on different substrates.
复制标题
DPY30 作为 ASH2L 特异性稳定剂，刺激 MLL 家族甲基转移酶在不同底物上的酶活性
DOI：
10.1016/j.isci.2022.104948
复制
发表时间：
2022-09-16
期刊：
影响因子：
5.8
通讯作者：
Chen, Yong
中科院分区：
文献类型：
--
作者：
Zhao, Lijie;Huang, Naizhe;Mencius, Jun;Li, Yanjing;Xu, Ying;Zheng, Yongxin;He, Wei;Li, Na;Zheng, Jun;Zhuang, Min;Quan, Shu;Chen, Yong
Dumpy-30（DPY 30）是混合谱系白血病（MLL）家族复合体的保守组分，并且对于MLL复合体的稳健甲基转移酶活性是必需的。然而，DPY 30在刺激MLL复合物的甲基转移酶活性中的生物化学作用仍然难以捉摸。在这里，我们证明DPY 30通过两种互补机制在调节MLL 1活性中起着至关重要的作用：核小体独立机制和核小体特异性机制。DPY 30作为ASH 2L特异性稳定剂发挥作用，以增加ASH 2L的稳定性并增强ASH 2L介导的相互作用。因此，DPY 30促进MLL 1复合物的压实和稳定，从而增加MLL 1复合物对不同底物的HKMT活性。DPY 30稳定的ASH 2L进一步获得了与H3和核小体DNA的额外界面，从而增强了核小体上MLL 1复合物的甲基转移酶活性。这些结果共同强调了DPY 30在MLL家族复合物的复合物组装和活性调节中的关键和保守作用。DPY 30刺激MLL复合物对广谱底物的酶活性DPY 30作为ASH 2L特异性稳定剂DPY 30促进MLL 1复合物的压实和稳定DPY 30稳定的ASH 2L获得与H3和核小体DNA的额外界面生物科学;生物化学;生物催化;生物工程
Dumpy-30 (DPY30) is a conserved component of the mixed lineage leukemia (MLL) family complex and is essential for robust methyltransferase activity of MLL complexes. However, the biochemical role of DPY30 in stimulating methyltransferase activity of MLL complexes remains elusive. Here, we demonstrate that DPY30 plays a crucial role in regulating MLL1 activity through two complementary mechanisms: A nucleosome-independent mechanism and a nucleosome-specific mechanism. DPY30 functions as an ASH2L-specific stabilizer to increase the stability of ASH2L and enhance ASH2L-mediated interactions. As a result, DPY30 promotes the compaction and stabilization of the MLL1 complex, consequently increasing the HKMT activity of the MLL1 complex on diverse substrates. DPY30-stabilized ASH2L further acquires additional interfaces with H3 and nucleosomal DNA, thereby boosting the methyltransferase activity of the MLL1 complex on nucleosomes. These results collectively highlight the crucial and conserved roles of DPY30 in the complex assembly and activity regulation of MLL family complexes. DPY30 stimulates the enzyme activity of MLL complexes on broad-spectrum substrates DPY30 functions as an ASH2L-specific stabilizer DPY30 promotes the compaction and stabilization of the MLL1 complex DPY30-stabilized ASH2L acquires additional interfaces with H3 and nucleosomal DNA Biological sciences; Biochemistry; Biocatalysis; Bioengineering
登录
查看更多内容
影响因子：
64.5
作者：
Hsu PL;Li H;Lau HT;Leonen C;Dhall A;Ong SE;Chatterjee C;Zheng N
通讯作者：
Zheng N
影响因子：
3
作者：
Kutzner, Carsten;Pall, Szilard;Fechner, Martin;Esztermann, Ansgar;de Groot, Bert L.;Grubmueller, Helmut
通讯作者：
Grubmueller, Helmut
影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
影响因子：
14.9
作者：
Kwon, Minjung;Park, Kihyun;Kim, Jaehoon
通讯作者：
Kim, Jaehoon
影响因子：
5.7
作者：
Haddad, John Faissal;Yang, Yidai;Couture, Jean-Francois
通讯作者：
Couture, Jean-Francois