This Article Full Text Full Text (PDF) Other Versions of this Article: MCB.01355-06v1 27/2/510    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Xia, Y. Articles by Lu, Z. Search for Related Content PubMed PubMed Citation Articles by Xia, Y. Articles by Lu, Z.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, January 2007, p. 510-517, Vol. 27, No. 2
0270-7306/07/$08.00+0     doi:10.1128/MCB.01355-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

MEKK1 Mediates the Ubiquitination and Degradation of c-Jun in Response to Osmotic Stress

Brain Tumor Center and Department of Neuro-Oncology,¹ Department of Thoracic and Cardiovascular Surgery,² Department of Molecular Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030,⁶ Signal Pharmaceuticals, LLC, San Diego, California 92121,³ Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599,⁴ Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037,⁵ The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas 77030⁷

Received 24 July 2006/ Returned for modification 22 September 2006/ Accepted 25 October 2006

c-Jun, a major transcription factor in the activating protein 1 family of regulatory proteins, is activated by many physiologic and pathological stimuli. We show here that c-Jun was downregulated in response to osmotic stress via ubiquitination-dependent degradation by the PHD/RING finger domain of MEKK1, which exhibited E3 ubiquitin ligase activity toward c-Jun in vitro and in vivo. The reduced c-Jun protein level resulting from exogenous expression of wild-type MEKK1 and the opposite effect induced by expression of a MEKK1 PHD/RING finger domain mutant were consistent with a higher level of c-Jun protein in MEKK1^–/– cells than in corresponding wild-type cells. The deficiency of MEKK1 blocked posttranslational downregulation of c-Jun in response to osmotic stress. Furthermore, apoptosis induced by osmotic stress was suppressed by overexpression of c-Jun, indicating that the downregulation of c-Jun promotes apoptosis.

Published ahead of print on 13 November 2006.

This article has been cited by other articles:

• Mokhtari, D., Myers, J. W., Welsh, N. (2008). The MAPK Kinase Kinase-1 Is Essential for Stress-Induced Pancreatic Islet Cell Death. Endocrinology 149: 3046-3053 [Abstract] [Full Text]  
• Sarma, K., Margueron, R., Ivanov, A., Pirrotta, V., Reinberg, D. (2008). Ezh2 Requires PHF1 To Efficiently Catalyze H3 Lysine 27 Trimethylation In Vivo. Mol. Cell. Biol. 28: 2718-2731 [Abstract] [Full Text]  
• Qi, X., Pohl, N. M., Loesch, M., Hou, S., Li, R., Qin, J.-Z., Cuenda, A., Chen, G. (2007). p38{alpha} Antagonizes p38{gamma} Activity through c-Jun-dependent Ubiquitin-proteasome Pathways in Regulating Ras Transformation and Stress Response. J. Biol. Chem. 282: 31398-31408 [Abstract] [Full Text]