The c-Jun N-terminal kinase (JNK) functions upstream of Aurora B to promote entry into mitosis

Kutluk Oktay, Erkan Buyuk, Ozgur Oktem, Maja H. Oktay, Filippo G. Giancotti

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Mitogen-activated protein kinases (MAPKs) are components of signaling cascades regulated by environmental stimuli. In addition to participating in the stress response, the MAPKs c-Jun N-terminal Kinases JNK1 and JNK2 regulate the proliferation of normal and neoplastic cells. JNKs contribute to these processes largely by phosphorylating c-Jun and thus contributing to the activation of the AP-1 complex. We here report that JNKs control entry into mitosis. We have observed that JNK activity and phosphorylation of c-Jun become elevated during the G2/M transition of the cell cycle in immortalized fibroblasts and ovarian granulosa cells. Pharmacological inhibition of JNK causes a profound cell cycle arrest at the G2/M transition in both cell types. This effect is specific as it occurs with two distinct small molecule compounds. Inactivation of JNK prior to mitosis prevents expression of Aurora B and phosphorylation of Histone-H3 at Ser 10. Silencing of JNK1 and 2 causes a similar effect, whereas overexpression of JNK1 and 2 causes the opposite effect. Inhibition of JNK delays activation of cdc-2 and prevents downregulation of Cyclin B1. We conclude that JNK signaling promotes entry into mitosis by promoting expression of Aurora B and thereby phosphorylation of Histone-H3.

Original languageEnglish (US)
Pages (from-to)533-541
Number of pages9
JournalCell Cycle
Volume7
Issue number4
StatePublished - Feb 15 2008

Fingerprint

JNK Mitogen-Activated Protein Kinases
Mitosis
Phosphorylation
Mitogen-Activated Protein Kinases
Histones
Chemical activation
Cells
G2 Phase Cell Cycle Checkpoints
Cyclin B1
Granulosa Cells
Transcription Factor AP-1
Fibroblasts
Cell Cycle
Down-Regulation
Pharmacology
Molecules

Keywords

  • Aurora-B
  • Cell cycle
  • JNK
  • Mitosis

ASJC Scopus subject areas

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Cite this

Oktay, K., Buyuk, E., Oktem, O., Oktay, M. H., & Giancotti, F. G. (2008). The c-Jun N-terminal kinase (JNK) functions upstream of Aurora B to promote entry into mitosis. Cell Cycle, 7(4), 533-541.

The c-Jun N-terminal kinase (JNK) functions upstream of Aurora B to promote entry into mitosis. / Oktay, Kutluk; Buyuk, Erkan; Oktem, Ozgur; Oktay, Maja H.; Giancotti, Filippo G.

In: Cell Cycle, Vol. 7, No. 4, 15.02.2008, p. 533-541.

Research output: Contribution to journalArticle

Oktay, K, Buyuk, E, Oktem, O, Oktay, MH & Giancotti, FG 2008, 'The c-Jun N-terminal kinase (JNK) functions upstream of Aurora B to promote entry into mitosis', Cell Cycle, vol. 7, no. 4, pp. 533-541.
Oktay, Kutluk ; Buyuk, Erkan ; Oktem, Ozgur ; Oktay, Maja H. ; Giancotti, Filippo G. / The c-Jun N-terminal kinase (JNK) functions upstream of Aurora B to promote entry into mitosis. In: Cell Cycle. 2008 ; Vol. 7, No. 4. pp. 533-541.
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