SUMOylation of FOXM1B alters its transcriptional activity on regulation of MiR-200 family and JNK1 in MCF7 human breast cancer cells.
SUMOylation of FOXM1B alters its transcriptional activity on regulation of MiR-200 family and JNK1 in MCF7 human breast cancer cells.
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DOI：
10.3390/ijms150610233
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发表时间：
2014-06-10
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;Liu R;Wang L;Nascimento L;Brennan VC;Yang WH
转录因子叉头盒蛋白M1（FOXM 1）是一个众所周知的主调节器，在控制DNA复制和有丝分裂，以及细胞增殖所必需的细胞周期途径。在FOXM 1的三种主要亚型中，FOXM 1B与肿瘤生长和转移高度相关。FOXM 1B的活性受翻译后修饰（PTM）如磷酸化的调节，但它是否受小泛素相关修饰物（SUMO）的修饰仍不清楚。本研究的目的是确定FOXM 1B是否被SUMO蛋白修饰，并确定FOXM 1B的SUMO修饰对其靶基因转录活性的影响。在这里，我们报告FOXM 1B是明确定义为SUMO靶蛋白在细胞水平。此外，SUMO化蛋白酶SENP 2显著降低FOXM 1B的SUMO化。值得注意的是，FOXM 1B在赖氨酸残基463处被选择性SUMO化。虽然FOXM 1B的SUMO化是完全抑制其靶基因MiR-200 b/c和p21所必需的，但FOXM 1B的SUMO化是JNK 1基因完全激活所必需的。总的来说，我们提供的证据表明，FOXM 1B的SUMO和SUMO修饰后的FOXM 1B在其靶基因活性的调节中起着功能性作用。
Transcription factor Forkhead Box Protein M1 (FOXM1) is a well-known master regulator in controlling cell-cycle pathways essential for DNA replication and mitosis, as well as cell proliferation. Among the three major isoforms of FOXM1, FOXM1B is highly associated with tumor growth and metastasis. The activities of FOXM1B are modulated by post-translational modifications (PTMs), such as phosphorylation, but whether it is modified by small ubiquitin-related modifier (SUMO) remains unknown. The aim of the current study was to determine whether FOXM1B is post-translationally modified by SUMO proteins and also to identify SUMOylation of FOXM1B on its target gene transcription activity. Here we report that FOXM1B is clearly defined as a SUMO target protein at the cellular levels. Moreover, a SUMOylation protease, SENP2, significantly decreased SUMOylation of FOXM1B. Notably, FOXM1B is selectively SUMOylated at lysine residue 463. While SUMOylation of FOXM1B is required for full repression of its target genes MiR-200b/c and p21, SUMOylation of FOXM1B is essential for full activation of JNK1 gene. Overall, we provide evidence that FOXM1B is post-translationally modified by SUMO and SUMOylation of FOXM1B plays a functional role in regulation of its target gene activities.
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影响因子：
14.9
作者：
Knouf EC;Garg K;Arroyo JD;Correa Y;Sarkar D;Parkin RK;Wurz K;O'Briant KC;Godwin AK;Urban ND;Ruzzo WL;Gentleman R;Drescher CW;Swisher EM;Tewari M
通讯作者：
Tewari M
影响因子：
4.8
作者：
Aukrust, Ingvild;Bjorkhaug, Lise;Njolstad, Pal R.
通讯作者：
Njolstad, Pal R.
影响因子：
4
作者：
Bao, Bin;Wang, Zhiwei;Ali, Shadan;Kong, Dejuan;Banerjee, Sanjeev;Ahmad, Aamir;Li, Yiwei;Azmi, Asfar S.;Miele, Lucio;Sarkar, Fazlul H.
通讯作者：
Sarkar, Fazlul H.
影响因子：
11.2
作者：
Kong X;Li L;Li Z;Le X;Huang C;Jia Z;Cui J;Huang S;Wang L;Xie K
通讯作者：
Xie K
SUMO1对DLX3的Sumoylation促进其转录活性。
影响因子：
4
作者：
Duverger, Olivier;Chen, Susie X.;Lee, Delia;Li, Tianwei;Chock, P. Boon;Morasso, Maria I.
通讯作者：
Morasso, Maria I.