HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 38, 40112-40121, September 17, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/38/40112    most recent M405481200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by MacCorkle, R. A. Articles by Tan, T.-H. Search for Related Content PubMed PubMed Citation Articles by MacCorkle, R. A. Articles by Tan, T.-H. Social Bookmarking                      What's this?

Inhibition of JNK2 Disrupts Anaphase and Produces Aneuploidy in Mammalian Cells^*

Rebecca A. MacCorkle and Tse-Hua Tan

From the Department of Immunology, Baylor College of Medicine, Houston, Texas 77030

The JNK family members JNK1 and JNK2 regulate tumor growth and are essential for transformation by oncogenes such as constitutively activated Ras. The mechanisms downstream of JNK that regulate cell cycle progression and transformation are unclear. Here we show that inhibition of JNK2, but not JNK1, with either a dominant-negative mutant, a pharmacological inhibitor, or RNA interference caused an accumulation of mammalian cells with 4N DNA content. When observed by immunofluorescence, these cells progressed to metaphase without apparent defects in spindle formation or chromosome alignment to the metaphase plate, suggesting that the 4N accumulation is a result of postmetaphase defects. Consistent with this prediction, when JNK activity was suppressed, we observed defects in central spindle formation and chromosome segregation during anaphase. In contrast, cyclin-dependent kinase 1 activity, cyclin B1 protein, and Polo-like kinase 1 protein turnover remained intact when JNK was inhibited. In addition, continued inhibition of JNK activity did not block reentry into subsequent cell cycles but instead resulted in polyploidy. This evidence suggests that JNK2 functions in maintaining the genomic stability of mammalian cells by signaling that is independent of cyclin-dependent kinase 1/cyclin B1 down-regulation.

Received for publication, May 17, 2004 , and in revised form, June 29, 2004.

^* This work was supported by National Institutes of Health Grants R01-CA87076 and R01-AI42532 and an American Institute for Cancer Research Grant (to T.-H. T.) and Department of Defense Breast Cancer Research Program Fellowship DAMD 17-00-1-0141 and National Institutes of Health Training Grant T32-AI07495 (to R. A. M.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Dept. of Immunology, Baylor College of Medicine, One Baylor Plaza, M929, Houston, TX 77030. Tel.: 713-798-4665; Fax: 713-798-3033; E-mail: ttan{at}bcm.tmc.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. Alter, D. Rozentzweig, and E. Bengal Inhibition of Myoblast Differentiation by Tumor Necrosis Factor {alpha} Is Mediated by c-Jun N-terminal Kinase 1 and Leukemia Inhibitory Factor J. Biol. Chem., August 22, 2008; 283(34): 23224 - 23234. [Abstract] [Full Text] [PDF]

				I-C. Wang, Y.-J. Chen, D. E. Hughes, T. Ackerson, M. L. Major, V. V. Kalinichenko, R. H. Costa, P. Raychaudhuri, A. L. Tyner, and L. F. Lau FoxM1 Regulates Transcription of JNK1 to Promote the G1/S Transition and Tumor Cell Invasiveness J. Biol. Chem., July 25, 2008; 283(30): 20770 - 20778. [Abstract] [Full Text] [PDF]