Sumoylation of TCF21 downregulates the transcriptional activity of estrogen receptor-alpha.
Sumoylation of TCF21 downregulates the transcriptional activity of estrogen receptor-alpha.
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TCF21 的苏酰化下调雌激素受体-α 的转录活性
DOI：
10.18632/oncotarget.8354
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发表时间：
2016-05-03
期刊：
影响因子：
--
通讯作者：
Wu H
中科院分区：
文献类型：
--
作者：
Ao X;Li S;Xu Z;Yang Y;Chen M;Jiang X;Wu H
异常雌激素受体-α（ERα）信号传导被认为是乳腺癌发展的主要因素。然而，乳腺癌中ERα调控的分子机制仍不确定。在本研究中，我们发现转录因子21（TCF 21）与ERα相互作用，并以HDACs依赖的方式抑制其转录活性。我们还发现TCF 21可以被小的泛素样修饰物SUMO 1 sumoylated，并且这种修饰可以被SENP 1逆转。TCF 21的Sumoylation发生在赖氨酸残基24（K24）处。用精氨酸取代K24导致sumoylation完全取消。类小泛素化稳定TCF 21，但不影响其亚细胞定位。TCF 21的SUMO化也增强了其与HDAC 1/2的相互作用，而不影响其与ERα的相互作用。此外，类小泛素化TCF 21促进其对ERα转录活性的抑制，并增加HDAC 1/2向pS2启动子的募集。与这些观察结果一致，TCF 21的sumoylation可以抑制ERα阳性乳腺癌细胞的生长，并降低细胞周期中S期细胞的比例。提示TCF 21可能是ERα的负调控因子，其SUMO化通过促进HDAC 1/2的募集而抑制ERα的转录活性。
Aberrant estrogen receptor-α (ERα) signaling is recognized as a major contributor to the development of breast cancer. However, the molecular mechanism underlying the regulation of ERα in breast cancer is still inconclusive. In this study, we showed that the transcription factor 21 (TCF21) interacted with ERα, and repressed its transcriptional activity in a HDACs-dependent manner. We also showed that TCF21 could be sumoylated by the small ubiquitin-like modifier SUMO1, and this modification could be reversed by SENP1. Sumoylation of TCF21 occurred at lysine residue 24 (K24). Substitution of K24 with arginine resulted in complete abolishment of sumoylation. Sumoylation stabilized TCF21, but did not affect its subcellular localization. Sumoylation of TCF21 also enhanced its interaction with HDAC1/2 without affecting its interaction with ERα. Moreover, sumoylation of TCF21 promoted its repression of ERα transcriptional activity, and increased the recruitment of HDAC1/2 to the pS2 promoter. Consistent with these observations, sumoylation of TCF21 could inhibit the growth of ERα-positive breast cancer cells and decreased the proportion of S-phase cells in the cell cycle. These findings suggested that TCF21 might act as a negative regulator of ERα, and its sumoylation inhibited the transcriptional activity of ERα through promoting the recruitment of HDAC1/2.
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影响因子：
4.6
作者：
Liu Y;Ao X;Jia Z;Bai XY;Xu Z;Hu G;Jiang X;Chen M;Wu H
通讯作者：
Wu H
影响因子：
5.8
作者：
Margueron, R;Duong, V;Cavaillès, V
通讯作者：
Cavaillès, V
GPS2 蛋白的 SUMO 化调节其转录抑制功能
影响因子：
3.3
作者：
Bi H;Li S;Wang M;Jia Z;Chang AK;Pang P;Wu H
通讯作者：
Wu H
影响因子：
14.9
作者：
Giamas G;Castellano L;Feng Q;Knippschild U;Jacob J;Thomas RS;Coombes RC;Smith CL;Jiao LR;Stebbing J
通讯作者：
Stebbing J
影响因子：
4.8
作者：
Ho, J.;Bassi, C.;Stambolic, V.
通讯作者：
Stambolic, V.