The emerging role of lysine methyltransferase SETD8 in human diseases

被引：71
|
作者：
Milite, Ciro [1 ,2 ]
Feoli, Alessandra [1 ,2 ,3 ]
Viviano, Monica [1 ,2 ]
Rescigno, Donatella [1 ,2 ,3 ]
Cianciulli, Agostino [1 ,2 ,3 ]
Balzano, Amodio Luca [1 ,2 ,3 ]
Mai, Antonello [4 ]
Castellano, Sabrina [1 ,2 ,5 ]
Sbardella, Gianluca [1 ,2 ]
机构：
[1] Univ Salerno, Dipartimento Farm, Via Giovanni Paolo 2 132, I-84084 Salerno, Italy
[2] Univ Salerno, Epigenet Med Chem Lab, Via Giovanni Paolo 2 132, I-84084 Salerno, Italy
[3] Univ Salerno, Programma Dottorato Ric Sci Farmaco, Via Giovanni Paolo 2 132, I-84084 Salerno, Italy
[4] Sapienza Univ Roma, Dipartimento Chim & Tecnol Farmaco, Ist Pasteur, Fdn Cenci Bolognetti, Ple A Moro 5, I-00185 Rome, Italy
[5] Univ Salerno, Dipartimento Med & Chirurg, Via Salvador Allende, I-84081 Salerno, Italy
来源：
CLINICAL EPIGENETICS | 2016年 / 8卷
关键词：
SMALL-MOLECULE INHIBITORS; 3' UNTRANSLATED REGION; MIR-502; BINDING-SITE; HISTONE H4-LYSINE 20; ACIDS B-E; CELL-CYCLE; PROTEIN METHYLTRANSFERASES; COMPETITIVE INHIBITOR; MIR-502-BINDING SITE; MARINE SEDIMENT;
D O I：
10.1186/s13148-016-0268-4
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
SETD8/SET8/Pr-SET7/KMT5A is the only known lysine methyltransferase (KMT) that monomethylates lysine 20 of histone H4 (H4K20) in vivo. Lysine residues of non-histone proteins including proliferating cell nuclear antigen (PCNA) and p53 are also monomethylated. As a consequence, the methyltransferase activity of the enzyme is implicated in many essential cellular processes including DNA replication, DNA damage response, transcription modulation, and cell cycle regulation. This review aims to provide an overview of the roles of SETD8 in physiological and pathological pathways and to discuss the progress made to date in inhibiting the activity of SETD8 by small molecules, with an emphasis on their discovery, selectivity over other methyltransferases and cellular activity.
引用
收藏
页数：15
相关论文
共 34 条
  • [1] The emerging role of lysine methyltransferase SETD8 in human diseases
    Ciro Milite
    Alessandra Feoli
    Monica Viviano
    Donatella Rescigno
    Agostino Cianciulli
    Amodio Luca Balzano
    Antonello Mai
    Sabrina Castellano
    Gianluca Sbardella
    Clinical Epigenetics, 2016, 8
  • [2] Progress in the Development of Lysine Methyltransferase SETD8 Inhibitors
    Milite, Ciro
    Feoli, Alessandra
    Viviano, Monica
    Rescigno, Donatella
    Mai, Antonello
    Castellano, Sabrina
    Sbardella, Gianluca
    CHEMMEDCHEM, 2016, 11 (16) : 1680 - 1685
  • [3] The dynamic conformational landscape of the protein methyltransferase SETD8
    Chen, Shi
    Wiewiora, Rafal P.
    Meng, Fanwang
    Babault, Nicolas
    Ma, Anqi
    Yu, Wenyu
    Qian, Kun
    Hu, Hao
    Zou, Hua
    Wang, Junyi
    Fan, Shijie
    Blum, Gil
    Pittella-Silva, Fabio
    Beauchamp, Kyle A.
    Tempel, Wolfram
    Jiang, Hualiang
    Chen, Kaixian
    Skene, Robert J.
    Zheng, Yujun George
    Brown, Peter J.
    Jin, Jian
    Luo, Cheng
    Chodera, John D.
    Luo, Minkui
    ELIFE, 2019, 8
  • [4] Structure-Based Design of a Covalent Inhibitor of the SET Domain-Containing Protein 8 (SETD8) Lysine Methyltransferase
    Butler, Kyle V.
    Ma, Anqi
    Yu, Wenyu
    Li, Fengling
    Tempel, Wolfram
    Babault, Nicolas
    Pittella-Silva, Fabio
    Shao, Jason
    Wang, Junyi
    Luo, Minkui
    Vedadi, Masoud
    Brown, Peter J.
    Arrowsmith, Cheryl H.
    Jin, Jian
    JOURNAL OF MEDICINAL CHEMISTRY, 2016, 59 (21) : 9881 - 9889
  • [5] Turning a Substrate Peptide into a Potent Inhibitor for the Histone Methyltransferase SETD8
    Judge, Russell A.
    Zhu, Haizhong
    Upadhyay, Anup K.
    Bodelle, Pierre M.
    Hutchins, Charles W.
    Torrent, Maricel
    Marin, Violeta L.
    Yu, Wenyu
    Vedadi, Masoud
    Li, Fengling
    Brown, Peter J.
    Pappano, William N.
    Sun, Chaohong
    Petros, Andrew M.
    ACS MEDICINAL CHEMISTRY LETTERS, 2016, 7 (12): : 1102 - 1106
  • [6] Histone Methyltransferase Setd8 Represses Gata2 Expression and Regulates Erythroid Maturation
    Malik, Jeffrey
    Getman, Michael
    Steiner, Laurie A.
    MOLECULAR AND CELLULAR BIOLOGY, 2015, 35 (12) : 2059 - 2072
  • [7] Small-Molecule Inhibitors of SETD8 with Cellular Activity
    Blum, Gil
    Ibanez, Glorymar
    Rao, Xiangjun
    Shum, David
    Radu, Constantin
    Djaballah, Hakim
    Rice, Judd C.
    Luo, Minkui
    ACS CHEMICAL BIOLOGY, 2014, 9 (11) : 2471 - 2478
  • [8] Structure-activity relationship studies of SETD8 inhibitors
    Ma, Anqi
    Yu, Wenyu
    Xiong, Yan
    Butler, Kyle V.
    Brown, Peter J.
    Jin, Jian
    MEDCHEMCOMM, 2014, 5 (12) : 1892 - 1898
  • [9] DMSO-Related Effects on Ligand-Binding Properties of Lysine Methyltransferases G9a and SETD8
    Feoli, Alessandra
    Sarno, Giuliana
    Castellano, Sabrina
    Sbardella, Gianluca
    CHEMBIOCHEM, 2024, 25 (04)
  • [10] The Use of Nucleosome Substrates Improves Binding of SAM Analogs to SETD8
    Strelow, John M.
    Xiao, Min
    Cavitt, Rachel N.
    Fite, Nathan C.
    Margolis, Brandon J.
    Park, Kyu-Jin
    JOURNAL OF BIOMOLECULAR SCREENING, 2016, 21 (08) : 786 - 794
1234