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

J. Biol. Chem., Vol. 281, Issue 21, 14691-14699, May 26, 2006

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 281/21/14691    most recent M600163200v1 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 Udayakumar, T. S. Articles by Fondell, J. D. Search for Related Content PubMed PubMed Citation Articles by Udayakumar, T. S. Articles by Fondell, J. D. Social Bookmarking                      What's this?

Regulation of Aurora-A Kinase Gene Expression via GABP Recruitment of TRAP220/MED1^*

From the Department of Physiology & Biophysics, Robert Wood Johnson Medical School, UMDNJ, Piscataway, New Jersey 08854

The TRAP/Mediator coactivator complex serves as a functional interface between DNA-bound transactivators and the RNA polymerase II-associated basal transcription apparatus. TRAP220/MED1 is a variably associated subunit of the complex that plays a specialized role in selectively targeting TRAP/Mediator to specific genes. Ablation of the Trap220/Med1 gene in mice impairs embryonic cell growth, yet the underlying mechanism is unknown. In this report, we identified distinct cell growth regulatory genes whose expression is affected by the loss of TRAP220/MED1 by RNA interference. Among the down-regulated genes revealed by cDNA microarray analyses, we identified Aurora-A, a centrosome kinase that plays a critical role in regulating M phase events and is frequently amplified in several types of cancer. In general, we found that TRAP220/MED1 expression is required for high basal levels of Aurora-A gene expression and that ectopic overexpression of TRAP220/MED1 coactivates transcription from the Aurora-A gene promoter. Furthermore, chromatin immunoprecipitation assays show that TRAP220/MED1-containing TRAP/Mediator complexes directly bind to the Aurora-A promoter in vivo. Finally, we present evidence suggesting that TRAP/Mediator is recruited to the Aurora-A gene via direct interactions between TRAP220/MED1 and the Ets-related transcription factor GABP. Taken together, these findings suggest that TRAP220/MED1 plays a novel coregulatory role in facilitating the recruitment of TRAP/Mediator to specific target genes involved in growth and cell cycle progression.

Received for publication, January 6, 2006 , and in revised form, March 24, 2006.

^* This work was supported by National Institutes of Health Grant DK54030-06 (to J. D. F.). 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.

The on-line version of this article (available at http://www.jbc.org) contains a supplemental data chart.

¹ To whom correspondence should be addressed. Tel.: 732-235-3348; Fax: 732-235-5823; E-mail: fondeljd{at}umdnj.edu.

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

This article has been cited by other articles:

				M. Yang, J. Hay, and W. T. Ruyechan Varicella-Zoster Virus IE62 Protein Utilizes the Human Mediator Complex in Promoter Activation J. Virol., December 15, 2008; 82(24): 12154 - 12163. [Abstract] [Full Text] [PDF]

				K. Wakahara, T. Ohno, M. Kimura, T. Masuda, S. Nozawa, T. Dohjima, T. Yamamoto, A. Nagano, G. Kawai, A. Matsuhashi, et al. EWS-Fli1 Up-Regulates Expression of the Aurora A and Aurora B Kinases Mol. Cancer Res., December 1, 2008; 6(12): 1937 - 1945. [Abstract] [Full Text] [PDF]

				L. He, H. Yang, Y. Ma, W. J. Pledger, W. D. Cress, and J. Q. Cheng Identification of Aurora-A as a Direct Target of E2F3 during G2/M Cell Cycle Progression J. Biol. Chem., November 7, 2008; 283(45): 31012 - 31020. [Abstract] [Full Text] [PDF]

				A. Klein, D. Flugel, and T. Kietzmann Transcriptional Regulation of Serine/Threonine Kinase-15 (STK15) Expression by Hypoxia and HIF-1 Mol. Biol. Cell, September 1, 2008; 19(9): 3667 - 3675. [Abstract] [Full Text] [PDF]

				L.-Y. Hung, J. T. Tseng, Y.-C. Lee, W. Xia, Y.-N. Wang, M.-L. Wu, Y.-H. Chuang, C.-H. Lai, and W.-C. Chang Nuclear epidermal growth factor receptor (EGFR) interacts with signal transducer and activator of transcription 5 (STAT5) in activating Aurora-A gene expression Nucleic Acids Res., August 1, 2008; 36(13): 4337 - 4351. [Abstract] [Full Text] [PDF]

				M. Belakavadi, P. K. Pandey, R. Vijayvargia, and J. D. Fondell MED1 Phosphorylation Promotes Its Association with Mediator: Implications for Nuclear Receptor Signaling Mol. Cell. Biol., June 15, 2008; 28(12): 3932 - 3942. [Abstract] [Full Text] [PDF]

				R. Vijayvargia, M. S. May, and J. D. Fondell A Coregulatory Role for the Mediator Complex in Prostate Cancer Cell Proliferation and Gene Expression Cancer Res., May 1, 2007; 67(9): 4034 - 4041. [Abstract] [Full Text] [PDF]

				S.-W. Dessie, F. Rings, M. Holker, M. Gilles, D. Jennen, E. Tholen, V. Havlicek, U. Besenfelder, V. L Sukhorukov, U. Zimmermann, et al. Dielectrophoretic behavior of in vitro-derived bovine metaphase II oocytes and zygotes and its relation to in vitro embryonic developmental competence and mRNA expression pattern Reproduction, May 1, 2007; 133(5): 931 - 946. [Abstract] [Full Text] [PDF]