The c-Jun N-terminal kinase (JNK) functions upstream of Aurora B to promote entry into mitosis Journal Article
| Authors: | Oktay, K.; Buyuk, E.; Oktem, O.; Oktay, M. H.; Giancotti, F. G. |
| Article Title: | The c-Jun N-terminal kinase (JNK) functions upstream of Aurora B to promote entry into mitosis |
| 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. ©2008 Landes Bioscience. |
| Keywords: | signal transduction; controlled study; protein expression; protein phosphorylation; nonhuman; flow cytometry; protein function; mitosis; cell cycle protein; animal cell; mouse; animals; mice; cell cycle; gene overexpression; enzyme inhibition; mitogen activated protein kinase p38; serine; rna interference; enzyme activity; phosphorylation; gene expression regulation; enzyme phosphorylation; cell transformation; protein-serine-threonine kinases; histone h3; enzyme inactivation; immunoblotting; fibroblast; cell cycle arrest; cell cycle g2 phase; cell cycle m phase; down regulation; cyclin b1; enzyme kinetics; histones; nih 3t3 cells; g2 phase; aurora b kinase; bromodeoxyuridine; functional proteomics; aurora-b; jnk mitogen-activated protein kinases; cell immortalization; jnk; anthra[1,9 cd]pyrazol 6(2h) one; stress activated protein kinase 1; granulosa cell; granulosa cells |
| Journal Title: | Cell Cycle |
| Volume: | 7 |
| Issue: | 4 |
| ISSN: | 1538-4101 |
| Publisher: | Taylor & Francis Inc. |
| Date Published: | 2008-02-15 |
| Start Page: | 533 |
| End Page: | 541 |
| Language: | English |
| PUBMED: | 18431843 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 10" - "Export Date: 17 November 2011" - "Source: Scopus" |
