title: JNK1 and 2 play a negative role in reprogramming to pluripotent stem cells by suppressing Klf4 activity.
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.
authors.affiliation: The Hormel Institute, University of Minnesota, 801, 16th Ave, NE, Austin, MN 55912, USA.
authors.forename: Ke
authors.initials: K
authors.lastname: Yao
authors.affiliation: The Hormel Institute, University of Minnesota, 801, 16th Ave, NE, Austin, MN 55912, USA.
authors.forename: Myoung Ok
authors.initials: MO
authors.lastname: Ki
authors.affiliation: The Hormel Institute, University of Minnesota, 801, 16th Ave, NE, Austin, MN 55912, USA.
authors.forename: Hanyong
authors.initials: H
authors.lastname: Chen
authors.affiliation: The Hormel Institute, University of Minnesota, 801, 16th Ave, NE, Austin, MN 55912, USA.
authors.forename: Yong-Yeon
authors.initials: YY
authors.lastname: Cho
authors.affiliation: The Hormel Institute, University of Minnesota, 801, 16th Ave, NE, Austin, MN 55912, USA.
authors.forename: Sung-Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: The Hormel Institute, University of Minnesota, 801, 16th Ave, NE, Austin, MN 55912, USA.
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Yu
authors.affiliation: The Hormel Institute, University of Minnesota, 801, 16th Ave, NE, Austin, MN 55912, USA.
authors.forename: Sung-Young
authors.initials: SY
authors.lastname: Lee
authors.affiliation: The Hormel Institute, University of Minnesota, 801, 16th Ave, NE, Austin, MN 55912, USA.
authors.forename: Kun-Yeong
authors.initials: KY
authors.lastname: Lee
authors.affiliation: The Hormel Institute, University of Minnesota, 801, 16th Ave, NE, Austin, MN 55912, USA.
authors.forename: Kibeom
authors.initials: K
authors.lastname: Bae
authors.affiliation: The Hormel Institute, University of Minnesota, 801, 16th Ave, NE, Austin, MN 55912, USA.
authors.forename: Cong
authors.initials: C
authors.lastname: Peng
authors.affiliation: The Hormel Institute, University of Minnesota, 801, 16th Ave, NE, Austin, MN 55912, USA.
authors.forename: Do Young
authors.initials: DY
authors.lastname: Lim
authors.affiliation: The Hormel Institute, University of Minnesota, 801, 16th Ave, NE, Austin, MN 55912, USA.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Bode
authors.affiliation: The Hormel Institute, University of Minnesota, 801, 16th Ave, NE, Austin, MN 55912, USA.
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D065150:Cellular Reprogramming; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D053605:Leukemia Inhibitory Factor / Q000494:pharmacology; D051379:Mice; D048055:Mitogen-Activated Protein Kinase 8 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D048056:Mitogen-Activated Protein Kinase 9 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000873:Anthracenes; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D053605:Leukemia Inhibitory Factor; D034741:RNA, Small Interfering; D014157:Transcription Factors; C432165:pyrazolanthrone; D048056:Mitogen-Activated Protein Kinase 9; D048055:Mitogen-Activated Protein Kinase 8