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

Kyunghee Lee, Kiwon Song

Research output: Contribution to journalArticle

20 Citations (Scopus)

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 G2/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 G2/M is tightly coupled with histone H3 phosphorylation. Basal JNKs were able to phosphorylate histone H3 in vitro and co-precipitation of histone H3 and JNKs was only detected at G2/M. Taken together, these data strongly suggest that basal JNKs play a key role in controlling histone H3 phosphorylation for mitotic entry at G2/M phase.

Original languageEnglish
Pages (from-to)216-221
Number of pages6
JournalCell Cycle
Volume7
Issue number2
DOIs
Publication statusPublished - 2008 Jan 15

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JNK Mitogen-Activated Protein Kinases
Histones
Phosphotransferases
Phosphorylation
Serine
G2 Phase
Cell Division
Cyclin A
Centrosome
RNA Interference
Mitosis
Fibroblasts

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

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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 G2/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 G2/M is tightly coupled with histone H3 phosphorylation. Basal JNKs were able to phosphorylate histone H3 in vitro and co-precipitation of histone H3 and JNKs was only detected at G2/M. Taken together, these data strongly suggest that basal JNKs play a key role in controlling histone H3 phosphorylation for mitotic entry at G2/M phase.",
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Basal c-Jun N-terminal kinases promote mitotic progression through histone H3 phosphorylation. / Lee, Kyunghee; Song, Kiwon.

In: Cell Cycle, Vol. 7, No. 2, 15.01.2008, p. 216-221.

Research output: Contribution to journalArticle

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