Targeting protein lysine methylation and demethylation in cancers

被引:52
作者
He, Yunlong [2 ]
Korboukh, Ilia [1 ]
Jin, Jian [1 ]
Huang, Jing [2 ]
机构
[1] Univ N Carolina, Ctr Integrat Chem Biol & Drug Discovery, Chapel Hill, NC 27599 USA
[2] NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA
基金
美国国家卫生研究院;
关键词
methylation; demethylation; methyltransferase; demethylase; cancer; epigenetics; NF-KAPPA-B; G9A HISTONE METHYLTRANSFERASE; DOMAIN-CONTAINING PROTEINS; BREAST-CANCER; TRANSCRIPTIONAL REPRESSION; SELECTIVE INHIBITORS; CELL-PROLIFERATION; STRUCTURAL BASIS; PROSTATE-CANCER; SILENCED GENES;
D O I
10.1093/abbs/gmr109
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
During the last decade, we saw an explosion of studies investigating the role of lysine methylation/demethylation of histones and non-histone proteins, such as p53, NF-kappaB, and E2F1. These 'Ying-Yang' post-translational modifications are important to fine-tuning the activity of these proteins. Lysine methylation and demethylation are catalyzed by protein lysine methyl-transferases (PKMTs) and protein lysine demethylases (PKDMs). PKMTs, PKDMs, and their substrates have been shown to play important roles in cancers. Although the underlying mechanisms of tumorigenesis are still largely unknown, growing evidence is starting to link aberrant regulation of methylation to tumorigenesis. This review focuses on summarizing the recent progress in understanding of the function of protein lysine methylation, and in the discovery of small molecule inhibitors for PKMTs and PKDMs. We also discuss the potential and the caveats of targeting protein lysine methylation for the treatment of cancer.
引用
收藏
页码:70 / 79
页数:10
相关论文
共 101 条
[81]  
Tibodeau JD, 2009, ANTIOXID REDOX SIGN, V11, P1097, DOI [10.1089/ars.2008.2318, 10.1089/ARS.2008.2318]
[82]   Regulating the p53 pathway:: in vitro hypotheses, in vivo veritas [J].
Toledo, Franck ;
Wahl, Geoffrey M. .
NATURE REVIEWS CANCER, 2006, 6 (12) :909-923
[83]   Histone demethylation by a family of JmjC domain-containing proteins [J].
Tsukada, Y ;
Fang, J ;
Erdjument-Bromage, H ;
Warren, ME ;
Borchers, CH ;
Tempst, P ;
Zhang, Y .
NATURE, 2006, 439 (7078) :811-816
[84]   Identification of Cell-Active Lysine Specific Demethylase 1-Selective Inhibitors [J].
Ueda, Rie ;
Suzuki, Takayoshi ;
Mino, Koshiki ;
Tsumoto, Hiroki ;
Nakagawa, Hidehiko ;
Hasegawa, Makoto ;
Sasaki, Ryuzo ;
Mizukami, Tamio ;
Miyata, Naoki .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2009, 131 (48) :17536-17537
[85]   Dot1p modulates silencing in yeast by methylation of the nucleosome core [J].
van Leeuwen, F ;
Gafken, PR ;
Gottschling, DE .
CELL, 2002, 109 (06) :745-756
[86]   The polycomb group protein EZH2 is involved in progression of prostate cancer [J].
Varambally, S ;
Dhanasekaran, SM ;
Zhou, M ;
Barrette, TR ;
Kumar-Sinha, C ;
Sanda, MG ;
Ghosh, D ;
Pienta, KJ ;
Sewalt, RGAB ;
Otte, AP ;
Rubin, MA ;
Chinnaiyan, AM .
NATURE, 2002, 419 (6907) :624-629
[87]  
Vedadi M, 2011, NAT CHEM BIOL, V7, P566, DOI [10.1038/NCHEMBIO.599, 10.1038/nchembio.599]
[88]   Purification and functional characterization of a histone H3-lysine 4-specific methyltransferase [J].
Wang, HB ;
Cao, R ;
Xia, L ;
Erdjument-Bromage, H ;
Borchers, C ;
Tempst, P ;
Zhang, Y .
MOLECULAR CELL, 2001, 8 (06) :1207-1217
[89]   The lysine demethylase LSD1 (KDM1) is required for maintenance of global DNA methylation [J].
Wang, Jing ;
Hevi, Sarah ;
Kurash, Julia K. ;
Lei, Hong ;
Gay, Frederique ;
Bajko, Jeffrey ;
Su, Hui ;
Sun, Weitao ;
Chang, Hua ;
Xu, Guoliang ;
Gaudet, Francois ;
Li, En ;
Chen, Taiping .
NATURE GENETICS, 2009, 41 (01) :125-129
[90]   LSD1 Is a Subunit of the NuRD Complex and Targets the Metastasis Programs in Breast Cancer [J].
Wang, Yan ;
Zhang, Hua ;
Chen, Yupeng ;
Sun, Yimin ;
Yang, Fen ;
Yu, Wenhua ;
Liang, Jing ;
Sun, Luyang ;
Yang, Xiaohan ;
Shi, Lei ;
Li, Ruifang ;
Li, Yanyan ;
Zhang, Yu ;
Li, Qian ;
Yi, Xia ;
Shang, Yongfeng .
CELL, 2009, 138 (04) :660-672