Serine 347 Phosphorylation by JNKs Negatively Regulates OCT4 Protein Stability in Mouse Embryonic Stem Cells.
Serine 347 Phosphorylation by JNKs Negatively Regulates OCT4 Protein Stability in Mouse Embryonic Stem Cells.
复制标题
丝氨酸347 JNK的磷酸化对小鼠胚胎干细胞中的OCT4蛋白稳定性负调节。
DOI：
10.1016/j.stemcr.2017.10.017
复制
发表时间：
2017-12-12
影响因子：
5.9
通讯作者：
Dong Z
中科院分区：
文献类型：
--
作者：
Bae KB;Yu DH;Lee KY;Yao K;Ryu J;Lim DY;Zykova TA;Kim MO;Bode AM;Dong Z
POU转录因子OCT 4对于维持胚胎干细胞（ESC）的未分化状态和产生诱导多能干细胞（iPSC）至关重要，但其确切的作用机制仍知之甚少。在这里，我们研究了OCT 4磷酸化在ESCs生物学功能中的作用。我们观察到c-Jun N-末端激酶（JNKs）直接与OCT 4相互作用并在丝氨酸347处磷酸化OCT 4，这抑制了OCT 4的转录活性。此外，OCT 4的磷酸化诱导FBXW 8的结合，这降低了OCT 4蛋白的稳定性并增强了其蛋白酶体降解。我们还发现突变体OCT 4（S347 A）可能延迟小鼠ESCs的分化过程，并提高诱导iPSCs的效率。这些结果表明，通过JNK在丝氨酸347上磷酸化OCT 4在其稳定性、转录活性和小鼠ESC的自我更新中起重要作用。JNK与OCT 4相互作用并在丝氨酸347处磷酸化丝氨酸347磷酸化抑制OCT 4转录活性和稳定性FBXW 8可以与在丝氨酸347处磷酸化的OCT 4蛋白相互作用小鼠ESCs的分化在OCT 4（S347 A）存在下延迟在这篇文章中，Bae和同事表明JNK直接与OCT 4相互作用并在丝氨酸347处磷酸化OCT 4。这种磷酸化抑制小鼠ESC中OCT 4的转录活性和稳定性。突变体OCT 4（S347 A）可能延缓小鼠胚胎干细胞的分化过程，提高诱导多能干细胞的效率。
The POU transcription factor OCT4 is critical for maintaining the undifferentiated state of embryonic stem cells (ESCs) and generating induced pluripotent stem cells (iPSCs), but its precise mechanisms of action remain poorly understood. Here, we investigated the role of OCT4 phosphorylation in the biological functions of ESCs. We observed that c-Jun N-terminal kinases (JNKs) directly interacted with and phosphorylated OCT4 at serine 347, which inhibited the transcriptional activity of OCT4. Moreover, phosphorylation of OCT4 induced binding of FBXW8, which reduced OCT4 protein stability and enhanced its proteasomal degradation. We also found that the mutant OCT4 (S347A) might delay the differentiation process of mouse ESCs and enhance the efficiency of generating iPSCs. These results demonstrated that OCT4 phosphorylation on serine 347 by JNKs plays an important role in its stability, transcriptional activities, and self-renewal of mouse ESCs. JNKs interact with and phosphorylate OCT4 at serine 347 Serine 347 phosphorylation inhibits OCT4 transcriptional activity and stability FBXW8 can interact with the OCT4 protein phosphorylated at serine 347 The differentiation of mouse ESCs is delayed in the presence of OCT4 (S347A) In this article, Bae and colleagues show that JNKs directly interact with and phosphorylate OCT4 at serine 347. This phosphorylation inhibits the transcriptional activity and stability of OCT4 in mouse ESCs. The mutant OCT4 (S347A) might delay the differentiation process of mouse ESCs and enhance the efficiency of generating iPSCs.
登录
查看更多内容
影响因子：
16
作者：
Lin, Yuanji;Yang, Ying;Li, Weihua;Chen, Qi;Li, Jie;Pan, Xiao;Zhou, Lina;Liu, Changwei;Chen, Chunsong;He, Jianqin;Cao, Hongcui;Yao, Hangping;Zheng, Li;Xu, Xiaowei;Xia, Zongping;Ren, Jiangtao;Xiao, Lei;Li, Lanjuan;Shen, Binghui;Zhou, Honglin;Wang, Ying-Jie
通讯作者：
Wang, Ying-Jie
影响因子：
3.7
作者：
Saxe JP;Tomilin A;Schöler HR;Plath K;Huang J
通讯作者：
Huang J
影响因子：
5.5
作者：
Cai, Ning;Li, Mo;Izpisua Belmonte, Juan Carlos
通讯作者：
Izpisua Belmonte, Juan Carlos
影响因子：
64.5
作者：
Takahashi, Kazutoshi;Yamanaka, Shinya
通讯作者：
Yamanaka, Shinya
Wwp2，一种 E3 泛素连接酶，靶向转录因子 Oct-4 进行泛素化
影响因子：
4.8
作者：
Xu, HM;Liao, B;Ying, J
通讯作者：
Ying, J