Basal c-Jun N-terminal kinases promote mitotic progression through histone H3 phosphorylation.
Phosphorylation of histone H3 at serine 10 (S10) is essential for the onset of mitosis. Here, we show that basal c-Jun N-terminal kinases (JNKs) are required for mitotic histone H3-S10 phosphorylation in human primary fibroblast IMR90 cells. Inhibition of JNKs by specific pharmacologic inhibitors, expression of dominant-negative JNK1 and 2 mutants, or RNAi of JNK1 and 2 prevented phosphorylation of histone H3 at S10 in vivo. The JNK-specific inhibitor SP600125 blocked mitotic entry, as shown by its ability to prevent CDK1 dephosphorylation and cyclin A degradation. Basal JNK phosphorylation increased at G(2)/M phase, although total JNK protein levels remained unchanged. In addition, basal JNKs were localized in nuclei and centrosomes during this time, suggesting that the nuclear localization of JNKs during G(2)/M is tightly coupled with histone H3 phosphorylation. Basal JNKs were able to phosphorylate histone H3 in vitro and coprecipitation of histone H3 and JNKs was only detected at G(2)/M. Taken together, these data strongly suggest that basal JNKs play a key role in controlling histone H3 phosphorylation for mitotic entry at G(2)/M phase.
Lee
Kyunghee
K
Department of Biochemistry and Institute of Life Science and Biotechnology, College of Science, Yonsei University, Seoul, Korea.
Song
Kiwon
K
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D018929:Cell Culture Techniques; D002453:Cell Cycle; D002460:Cell Line; D049109:Cell Proliferation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D051379:Mice; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism*; D008938:Mitosis; D041681:NIH 3T3 Cells; D010766:Phosphorylation
D000873:Anthracenes; D004791:Enzyme Inhibitors; D006657:Histones; C432165:pyrazolanthrone; D048055:Mitogen-Activated Protein Kinase 8