Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 1588K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zhang, J. Y. Articles by Khavari, P. A. Search for Related Content PubMed PubMed Citation Articles by Zhang, J. Y. Articles by Khavari, P. A. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Social Bookmarking                            What's this?

CDK4 regulation by TNFR1 and JNK is required for NF-B–mediated epidermal growth control

¹ Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA 94304
² Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305

Correspondence to Paul A. Khavari: khavari{at}CMGM.stanford.edu

Abstract

Nuclear factor B (NF-B) mediates homeostatic growth inhibition in the epidermis, and a loss of NF-B function promotes proliferation and oncogenesis. To identify mechanisms responsible for these effects, we impaired NF-B action in the epidermis by three different genetic approaches, including conditional NF-B blockade. In each case, epidermal hyperplasia was accompanied by an increase in both protein levels and tissue distribution of the G1 cell cycle kinase, CDK4. CDK4 up-regulation required intact TNFR1 and c-Jun NH₂-terminal kinase (JNK) function. Cdk4 gene deletion concomitant with conditional NF-B blockade demonstrated that CDK4 is required for growth deregulation. Therefore, epidermal homeostasis depends on antagonist regulation of CDK4 expression by NF-B and TNFR1/JNK.

Abbreviations used in this paper: 4OHT, 4-hydoxytamoxifen; BMZ, basement membrane zone; ER, estrogen receptor; IB, inhibitor of B; JNK, c-Jun NH₂-terminal kinase; NF-B, nuclear factor B.

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

This article has been cited by other articles:

• Adler, A. S., Sinha, S., Kawahara, T. L.A., Zhang, J. Y., Segal, E., Chang, H. Y. (2007). Motif module map reveals enforcement of aging by continual NF-{kappa}B activity. Genes Dev. 21: 3244-3257 [Abstract] [Full Text]  
• Zhang, J. Y., Adams, A. E., Ridky, T. W., Tao, S., Khavari, P. A. (2007). Tumor Necrosis Factor Receptor 1/c-Jun-NH2-Kinase Signaling Promotes Human Neoplasia. Cancer Res. 67: 3827-3834 [Abstract] [Full Text]  
• Sayama, K., Hanakawa, Y., Nagai, H., Shirakata, Y., Dai, X., Hirakawa, S., Tokumaru, S., Tohyama, M., Yang, L., Sato, S., Shizuo, A., Hashimoto, K. (2006). Transforming Growth Factor-beta-activated Kinase 1 Is Essential for Differentiation and the Prevention of Apoptosis in Epidermis. J. Biol. Chem. 281: 22013-22020 [Abstract] [Full Text]  
• Omori, E., Matsumoto, K., Sanjo, H., Sato, S., Akira, S., Smart, R. C., Ninomiya-Tsuji, J. (2006). TAK1 Is a Master Regulator of Epidermal Homeostasis Involving Skin Inflammation and Apoptosis. J. Biol. Chem. 281: 19610-19617 [Abstract] [Full Text]  
• auf dem Keller, U., Huber, M., Beyer, T. A., Kumin, A., Siemes, C., Braun, S., Bugnon, P., Mitropoulos, V., Johnson, D. A., Johnson, J. A., Hohl, D., Werner, S. (2006). Nrf Transcription Factors in Keratinocytes Are Essential for Skin Tumor Prevention but Not for Wound Healing. Mol. Cell. Biol. 26: 3773-3784 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents