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

J. Biol. Chem., Vol. 281, Issue 26, 18069-18080, June 30, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/26/18069    most recent M512734200v1 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 McFie, P. J. Articles by Roesler, W. J. Search for Related Content PubMed PubMed Citation Articles by McFie, P. J. Articles by Roesler, W. J. Social Bookmarking                      What's this?

Identification of a Co-repressor That Inhibits the Transcriptional and Growth-Arrest Activities of CCAAT/Enhancer-binding Protein ^*

Pamela J. McFie, Guo-Li Wang, Nicholai A. Timchenko, Heather L. Wilson^¶, Xiaobin Hu, and William J. Roesler¹

From the Department of Biochemistry, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E5, Canada, the Department of Pathology and Huffington Center on Aging, Baylor College of Medicine, Houston, Texas 77030, and the ^¶Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E3, Canada

We used a yeast two-hybrid screening approach to identify novel interactors of CCAAT/enhancer-binding protein (C/EBP) that may offer insight into its mechanism of action and regulation. One clone obtained was that for CA150, a nuclear protein previously characterized as a transcriptional elongation factor. In this report, we show that CA150 is a widely expressed co-repressor of C/EBP proteins. Two-hybrid and co-immunoprecipitation analyses indicated that CA150 interacts with C/EBP. Overexpression of CA150 inhibited the transactivation produced by C/EBP and was also able to reverse the enhancing effect of the co-activator p300 on C/EBP-mediated transactivation. Analysis of C/EBP mutants indicated that CA150 interacts with C/EBP primarily through a domain spanning amino acids 135–150. Chromatin immunoprecipitation assays showed that CA150 was present on a promoter that is repressed by C/EBP but not present on a promoter that is activated by C/EBP. Finally, we showed that in cells in which growth arrest had been induced by ectopic expression of C/EBP, CA150 was able to release them from growth arrest. Interestingly, CA150 could not reverse the growth arrest produced by the minimal growth-arrest domain of C/EBP (amino acids 175–217), suggesting that the effect of CA150 was directed at a region of C/EBP outside of this minimal domain, consistent with our two-hybrid analysis. Taken together, these data indicate that CA150 is a co-repressor of C/EBP proteins and provides a possible mechanism for how C/EBP can repress transcription of specific genes.

Received for publication, November 29, 2005 , and in revised form, April 20, 2006.

^* This work was supported by a graduate studentship award (to H. L. W.) from the Canadian Institutes of Health Research, a research grant (to W. J. R.) from the Canadian Institutes of Health Research/Saskatchewan Health Regional Partnership Program, and National Institutes of Health Grant GM55188 R01 (to N. A. T.). 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.

¹ To whom correspondence should be addressed: Dept. of Biochemistry, University of Saskatchewan, 107 Wiggins Rd., Saskatoon, Saskatchewan S7N 5E5, Canada. Tel.: 306-966-4375; Fax: 306-966-4390; E-mail: bill.roesler{at}usask.ca.

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

This article has been cited by other articles:

				G.-L. Wang, X. Shi, E. Salisbury, Y. Sun, J. H. Albrecht, R. G. Smith, and N. A. Timchenko Growth Hormone Corrects Proliferation and Transcription of Phosphoenolpyruvate Carboxykinase in Livers of Old Mice via Elimination of CCAAT/Enhancer-binding Protein {alpha}-Brm Complex J. Biol. Chem., January 12, 2007; 282(2): 1468 - 1478. [Abstract] [Full Text] [PDF]