JNK1 and 2 play a negative role in reprogramming to pluripotent stem cells by suppressing Klf4 activity
Copyright policy )JNK1 and 2 play a negative role in reprogramming to pluripotent stem cells by suppressing Klf4 activity
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.
- University of Minnesota United States
- University of Minnesota Morris United States
- University of Minnesota System United States
QH301-705.5, Molecular Sequence Data, Kruppel-Like Transcription Factors, Leukemia Inhibitory Factor, Kruppel-Like Factor 4, Mice, Animals, Humans, Mitogen-Activated Protein Kinase 9, Mitogen-Activated Protein Kinase 8, Amino Acid Sequence, Biology (General), Phosphorylation, RNA, Small Interfering, Embryonic Stem Cells, Medicine(all), Anthracenes, Cell Biology, Cellular Reprogramming, HEK293 Cells, RNA Interference, Developmental Biology, Protein Binding, Signal Transduction, Transcription Factors
QH301-705.5, Molecular Sequence Data, Kruppel-Like Transcription Factors, Leukemia Inhibitory Factor, Kruppel-Like Factor 4, Mice, Animals, Humans, Mitogen-Activated Protein Kinase 9, Mitogen-Activated Protein Kinase 8, Amino Acid Sequence, Biology (General), Phosphorylation, RNA, Small Interfering, Embryonic Stem Cells, Medicine(all), Anthracenes, Cell Biology, Cellular Reprogramming, HEK293 Cells, RNA Interference, Developmental Biology, Protein Binding, Signal Transduction, Transcription Factors
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