FOXP3 Activates SUMO-Conjugating UBC9 Gene in MCF7 Breast Cancer Cells.
FOXP3 Activates SUMO-Conjugating UBC9 Gene in MCF7 Breast Cancer Cells.
复制标题
DOI：
10.3390/ijms19072036
复制
发表时间：
2018-07-13
影响因子：
5.6
通讯作者：
Yang WH
中科院分区：
文献类型：
--
作者：
Wang CM;Yang WH;Liu R;Wang L;Yang WH
叉头盒蛋白P3（FOXP 3）是FOX蛋白家族的一种转录因子，主要参与调节性T（Treg）细胞的发育，并作为肿瘤抑制因子发挥作用。尽管FOXP 3在免疫系统和癌症发展中已被广泛研究，但其在UBC 9基因（SUMO化的唯一E2酶）调节中的功能尚不清楚。在此，我们发现FOXP 3在人MCF 7乳腺癌细胞中的过表达增加了UBC 9 mRNA的水平。此外，在FOXP 3-Tet-off MCF 7细胞中，UBC 9蛋白质的水平剂量依赖性地增加。值得注意的是，在MCF 7和HEK 293细胞中，FOXP 3以剂量依赖性方式激活UBC 9的启动子活性。接下来，通过定位UBC 9启动子以及定点突变和ChIP分析，我们表明FOXP 3激活UBC 9主要需要-310 bp区域的FOXP 3响应元件，而不是-2182 bp区域。最后，我们证明了FOXP 3的磷酸化（S418 A和Y342 F）的去除和乙酰化/泛素化（K263 R和K263 RK 268 R）的去除导致UBC 9的转录活性减弱。总之，FOXP 3作为一种新的转录激活因子的人UBC 9基因，这表明FOXP 3可能具有生理功能，作为一个新的球员在全球SUMO化，以及其他翻译后修饰系统。
Forkhead Box Protein P3 (FOXP3), a transcription factor of the FOX protein family, is essentially involved in the development of regulatory T (Treg) cells, and functions as a tumor suppressor. Although FOXP3 has been widely studied in immune system and cancer development, its function in the regulation of the UBC9 gene (for the sole E2 enzyme of SUMOylation) is unknown. Herein, we find that the overexpression of FOXP3 in human MCF7 breast cancer cells increases the level of UBC9 mRNA. Moreover, the level of UBC9 protein dose-dependently increases in the FOXP3-Tet-off MCF7 cells. Notably, the promoter activity of the UBC9 is activated by FOXP3 in a dose-dependent manner in both the MCF7 and HEK293 cells. Next, by mapping the UBC9 promoter as well as the site-directed mutagenesis and ChIP analysis, we show that the FOXP3 response element at the −310 bp region, but not the −2182 bp region, is mainly required for UBC9 activation by FOXP3. Finally, we demonstrate that the removal of phosphorylation (S418A and Y342F) and the removal of acetylation/ubiquitination (K263R and K263RK268R) of the FOXP3 result in attenuated transcriptional activity of UBC9. Taken together, FOXP3 acts as a novel transcriptional activator of the human UBC9 gene, suggesting that FOXP3 may have physiological functions as a novel player in global SUMOylation, as well as other post-translational modification systems.
登录
查看更多内容
影响因子：
11.2
作者：
Li W;Wang L;Katoh H;Liu R;Zheng P;Liu Y
通讯作者：
Liu Y
影响因子：
11.2
作者：
Liu R;Yi B;Wei S;Yang WH;Hart KM;Chauhan P;Zhang W;Mao X;Liu X;Liu CG;Wang L
通讯作者：
Wang L
MicroRNA-155 由 FOXP3 通过 BRCA1 转录抑制诱导，与人类乳腺癌的肿瘤发生相关
影响因子：
--
作者：
Gao S;Wang Y;Wang M;Li Z;Zhao Z;Wang RX;Wu R;Yuan Z;Cui R;Jiao K;Wang L;Ouyang L;Liu R
通讯作者：
Liu R
影响因子：
5.6
作者：
Wang CM;Liu R;Wang L;Nascimento L;Brennan VC;Yang WH
通讯作者：
Yang WH
影响因子：
30.8
作者：
Wildin, RS;Ramsdell, F;Brunkow, ME
通讯作者：
Brunkow, ME