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Basal c-Jun N-terminal kinases promote mitotic progression through histone H3 phosphorylation

Authors
 Kyunghee Lee  ;  Kiwon Song 
Citation
 CELL CYCLE, Vol.7(2) : 216-221, 2008 
Journal Title
 CELL CYCLE 
ISSN
 1538-4101 
Issue Date
2008
MeSH
Animals ; Anthracenes/pharmacology ; Cell Culture Techniques ; Cell Cycle ; Cell Line ; Cell Proliferation ; Enzyme Inhibitors/pharmacology ; Fibroblasts/cytology ; Fibroblasts/metabolism ; Histones/metabolism* ; Humans ; Mice ; Mitogen-Activated Protein Kinase 8/metabolism* ; Mitosis* ; NIH 3T3 Cells ; Phosphorylation
Keywords
basal JNKs ; SP600125 ; mitosis ; histone H3 ; IMR90
Abstract
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.
Files in This Item:
T200803564.pdf Download
DOI
10.4161/cc.7.2.5155
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Physiology (생리학교실) > 1. Journal Papers
Yonsei Authors
Lee, Kyung Hee(이경희)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/108209
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