Connections between TET proteins and aberrant DNA modification in cancer.
Connections between TET proteins and aberrant DNA modification in cancer.
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DOI：
10.1016/j.tig.2014.07.005
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发表时间：
2014-10
期刊：
影响因子：
--
通讯作者：
Rao A
中科院分区：
文献类型：
--
作者：
Huang Y;Rao A
DNA甲基化与癌症中肿瘤抑制基因的异常沉默有关，DNA甲基化/去甲基化周期的不平衡与肿瘤的发生和进展密切相关。泰特（ten-eleven translocation）蛋白是Fe（II）和2-酮戊二酸依赖性双加氧酶，其连续地将5-甲基胞嘧啶（5 mC）氧化为5-羟甲基胞嘧啶（5 hmC）、5-甲酰基胞嘧啶（5 fC）和5-羧基胞嘧啶（5caC），从而介导活性DNA去甲基化。本文就泰特蛋白和5 hmC在肿瘤中的病理生理作用作一综述。本文综述了恶性血液病和实体瘤中泰特蛋白的功能缺失突变和异常表达及调控，并讨论了评估泰特突变和5 hmC水平对癌症患者预后的潜在价值。我们还解决了泰特和两个关键酶参与细胞代谢，OGT和IDH之间的串扰。最后，我们讨论了靶向泰特蛋白和异常DNA甲基化在癌症中的治疗潜力。
DNA methylation has been linked to aberrant silencing of tumor suppressor genes in cancer, and an imbalance in DNA methylation/demethylation cycles is intimately implicated in the onset and progression of tumors. TET (ten-eleven translocation) proteins are Fe(II) and 2-oxoglutarate dependent dioxygenases that successively oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), thereby mediating active DNA demethylation. In this review, we focus on the pathophysiological role of TET proteins and 5hmC in cancer. We present an overview of loss-of-function mutations and abnormal expression and regulation of TET proteins in hematological malignancies and solid tumors, and discuss the potential prognostic value of assessing TET mutations and 5hmC levels in cancer patients. We also address the crosstalk between TET and two critical enzymes involved in cell metabolism, OGT and IDH. Lastly, we discuss the therapeutic potential of targeting TET proteins and aberrant DNA methylation in cancer.
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影响因子：
30.8
作者：
Busque L;Patel JP;Figueroa ME;Vasanthakumar A;Provost S;Hamilou Z;Mollica L;Li J;Viale A;Heguy A;Hassimi M;Socci N;Bhatt PK;Gonen M;Mason CE;Melnick A;Godley LA;Brennan CW;Abdel-Wahab O;Levine RL
通讯作者：
Levine RL
影响因子：
23.9
作者：
Dawlaty, Meelad M.;Ganz, Kibibi;Powell, Benjamin E.;Hu, Yueh-Chiang;Markoulaki, Styliani;Cheng, Albert W.;Gao, Qing;Kim, Jongpil;Choi, Sang-Woon;Page, David C.;Jaenisch, Rudolf
通讯作者：
Jaenisch, Rudolf
影响因子：
50.3
作者：
Figueroa ME;Abdel-Wahab O;Lu C;Ward PS;Patel J;Shih A;Li Y;Bhagwat N;Vasanthakumar A;Fernandez HF;Tallman MS;Sun Z;Wolniak K;Peeters JK;Liu W;Choe SE;Fantin VR;Paietta E;Löwenberg B;Licht JD;Godley LA;Delwel R;Valk PJ;Thompson CB;Levine RL;Melnick A
通讯作者：
Melnick A
影响因子：
11.8
作者：
Dawlaty, Meelad M.;Breiling, Achim;Le, Thuc;Raddatz, Guenter;Barrasa, M. Inmaculada;Cheng, Albert W.;Gao, Qing;Powell, Benjamin E.;Li, Zhe;Xu, Mingjiang;Faull, Kym F.;Lyko, Frank;Jaenisch, Rudolf
通讯作者：
Jaenisch, Rudolf
DOI：
10.1084/jem.20131141
发表时间：
2013-11-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Abdel-Wahab O;Gao J;Adli M;Dey A;Trimarchi T;Chung YR;Kuscu C;Hricik T;Ndiaye-Lobry D;Lafave LM;Koche R;Shih AH;Guryanova OA;Kim E;Li S;Pandey S;Shin JY;Telis L;Liu J;Bhatt PK;Monette S;Zhao X;Mason CE;Park CY;Bernstein BE;Aifantis I;Levine RL
通讯作者：
Levine RL