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  • Title: JNK1 and 2 play a negative role in reprogramming to pluripotent stem cells by suppressing Klf4 activity.
    Author: Yao K, Ki MO, Chen H, Cho YY, Kim SH, Yu DH, Lee SY, Lee KY, Bae K, Peng C, Lim DY, Bode AM, Dong Z.
    Journal: Stem Cell Res; 2014 Jan; 12(1):139-52. PubMed ID: 24211391.
    Abstract:
    Embryonic stem (ES) cells are pluripotent cells with the capacity for unlimited self-renewal or differentiation. Inhibition of MAPK pathways enhances mouse ES cell pluripotency characteristics. Compared to wildtype ES cells, jnk2(-/-) ES cells displayed a much higher growth rate. To determine whether JNKs are required for stem cell self-renewal or differentiation, we performed a phosphorylation kinase array assay to compare mouse ES cells under LIF+ or LIF- culture conditions. The data showed that activation of JNKs was induced by LIF withdrawal. We also found that JNK1 or 2 phosphorylated Klf4 at threonines 224 and 225. Activation of JNK signaling and phosphorylation of Klf4 inhibited Klf4 transcription and transactivation activity. Importantly, jnk1(-/-) and jnk2(-/-) murine embryonic fibroblasts (MEFs) exhibited a significantly greater potency in the ability to increase the number of iPS colonies compared with jnk wildtype MEFs. Overall, our results demonstrated that JNK1 and 2 play a negative role in reprogramming to pluripotent stem cells by suppressing Klf4 activity.
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