Dysregulated transcriptional and post-translational control of DNA methyltransferases in cancer.
Dysregulated transcriptional and post-translational control of DNA methyltransferases in cancer.
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DOI：
10.1186/2045-3701-4-46
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发表时间：
2014
影响因子：
7.5
通讯作者：
Wang YC
中科院分区：
文献类型：
--
作者：
Lin RK;Wang YC
癌症是全球死亡的主要原因。与肿瘤抑制基因相关的CpG岛的异常启动子高甲基化可导致转录沉默并导致肿瘤发生。DNA甲基转移酶（DNMT）是负责DNA甲基化的酶，并且已经报道在各种癌症中过度表达。本文综述了DNMT表达和活性的转录和翻译后调控的现状，重点关注肿瘤发生中的调控异常。DNMT基因表达的转录上调可由Ras-c-Jun信号通路、Sp1和Sp3锌指蛋白以及病毒癌蛋白诱导。还报道了p53、RB和FOXO 3a转录调节因子和辅抑制因子对DNMT基因的转录抑制。此外，microRNA 29家族、143、148 a和152的低表达与各种癌症中DNMT的过表达相关。已经报道了几种重要的翻译后修饰，包括乙酰化和磷酸化，以介导DNMT特别是DNMT 1的蛋白质稳定性和活性。在这篇综述中，我们还讨论了靶向DNMT蛋白表达和激活的药物用于癌症治疗策略。
Cancer is a leading cause of death worldwide. Aberrant promoter hypermethylation of CpG islands associated with tumor suppressor genes can lead to transcriptional silencing and result in tumorigenesis. DNA methyltransferases (DNMTs) are the enzymes responsible for DNA methylation and have been reported to be over-expressed in various cancers. This review highlights the current status of transcriptional and post-translational regulation of the DNMT expression and activity with a focus on dysregulation involved in tumorigenesis. The transcriptional up-regulation of DNMT gene expression can be induced by Ras-c-Jun signaling pathway, Sp1 and Sp3 zinc finger proteins and virus oncoproteins. Transcriptional repression on DNMT genes has also been reported for p53, RB and FOXO3a transcriptional regulators and corepressors. In addition, the low expressions of microRNAs 29 family, 143, 148a and 152 are associated with DNMTs overexpression in various cancers. Several important post-translational modifications including acetylation and phosphorylation have been reported to mediate protein stability and activity of the DNMTs especially DNMT1. In this review, we also discuss drugs targeting DNMT protein expression and activation for therapeutic strategy against cancer.
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影响因子：
2.8
作者：
Cui, Min;Wen, Zeqing;Wang, Fei
通讯作者：
Wang, Fei
DOI：
10.1073/pnas.0707628104
发表时间：
2007-10-02
影响因子：
11.1
作者：
Fabbri, Muller;Garzon, Ramiro;Croce, Carlo M.
通讯作者：
Croce, Carlo M.
影响因子：
30.8
作者：
Costello, JF;Fr端hwald, MC;Plass, C
通讯作者：
Plass, C
影响因子：
11.4
作者：
Fuks, F;Burgers, WA;Kouzarides, T
通讯作者：
Kouzarides, T
影响因子：
5.6
作者：
Fatemi, M;Hermann, A;Jeltsch, A
通讯作者：
Jeltsch, A