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

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

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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.

Authors

Kutluk Oktay

New York Medical College; Valhalla, NY

Erkan Buyuk

New York Medical College; Valhalla, NY

Ozgur Oktem

New York Medical College; Valhalla, NY

Maja Oktay

Montefiore Medical Center; Bronx, NY

Filippo G. Giancotti

Memorial Sloan-Kettering Cancer Center; New York, NY

Purchase article for $19

Subscribe to this journal for $129/year