p53-dependent autophagic degradation of TET2 modulates cancer therapeutic resistance.
p53-dependent autophagic degradation of TET2 modulates cancer therapeutic resistance.
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DOI：
10.1038/s41388-018-0524-5
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发表时间：
2019-03
期刊：
影响因子：
8
通讯作者：
Huang Y
中科院分区：
文献类型：
--
作者：
Zhang J;Tan P;Guo L;Gong J;Ma J;Li J;Lee M;Fang S;Jing J;Johnson G;Sun D;Cao WM;Dashwood R;Han L;Zhou Y;Dong WG;Huang Y
Tumor cells with p53 inactivation frequently exhibit chemotherapy resistance, which poses a longstanding challenge to cancer treatment. Here we unveiled a previously unrecognized role of TET2 in mediating p53-loss induced chemotherapy resistance in colon cancer. Deletion of TET2 in p53KO colon cancer cells enhanced DNA damage and restored chemotherapy sensitivity. By taking a two-pronged approach that combined pharmacological inhibition with genetic depletion, we discovered that p53 destabilized TET2 at protein level by promoting its autophagic degradation. At the molecular level, we further revealed a physical association between TET2 and p53 that facilitated the nucleoplasmic shuttling of TET2, as well as its recruitment to the autophagosome for degradation. Our study has unveiled a functional interplay between TET2 and p53 during anti-cancer therapy. Our findings establish the rationale for targeting TET2 to overcome chemotherapy resistance associated with mutant p53 tumors.
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影响因子：
16
作者：
Nakagawa, Tadashi;Lv, Lei;Nakagawa, Makiko;Yu, Yanbao;Yu, Chao;D'Alessio, Ana C.;Nakayama, Keiko;Fan, Heng-Yu;Chen, Xian;Xiong, Yue
通讯作者：
Xiong, Yue
影响因子：
11.5
作者：
Boyer, J;McLean, EG;Johnston, PG
通讯作者：
Johnston, PG
影响因子：
16.6
作者：
An J;González-Avalos E;Chawla A;Jeong M;López-Moyado IF;Li W;Goodell MA;Chavez L;Ko M;Rao A
通讯作者：
Rao A
DOI：
10.1016/j.tig.2014.07.005
发表时间：
2014-10
期刊：
Trends in genetics : TIG
影响因子：
--
作者：
Huang Y;Rao A
通讯作者：
Rao A
影响因子：
158.5
作者：
Delhommeau, Francois;Dupont, Sabrina;Bernard, Olivier A.
通讯作者：
Bernard, Olivier A.