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Originally published In Press as doi:10.1074/jbc.C000909200 on March 21, 2001

J. Biol. Chem., Vol. 276, Issue 20, 16597-16600, May 18, 2001
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ACCELERATED PUBLICATION
Tip60 and HDAC7 Interact with the Endothelin Receptor A and May Be Involved in Downstream Signaling*

He-Jin LeeDagger , Miyoung Chun§, and Konstantin V. Kandror

From the Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118

Endothelins exert their biological effects through G protein-coupled receptors. However, the precise mechanism of downstream signaling and trafficking of the receptors is largely unknown. Here we report that the histone acetyltransferase Tip60 and the histone deacetylase HDAC7 interact with one of the ET receptors, ETA, as determined by yeast two-hybrid analysis, glutathione S-transferase pull-down assays, and co-immunoprecipitation from transfected COS-7 cells. In the absence of ET-1, Tip60 and HDAC7 were localized mainly in the cell nucleus while ETA was predominantly confined to the plasma membrane. Stimulation with ET-1 resulted in the internalization of ETA to the perinuclear compartment and simultaneously in the efflux of Tip60 and HDAC7 from the nucleus to the same perinuclear compartment where each protein co-localized with the receptor. Upon co-transfection with ETA into COS-7 cells, Tip60 strongly increased ET-1-induced ERK1/2 phosphorylation, whereas HDAC7 had no significant effect. We thus suggest that protein acetylase and deacetylase interact with ETA in a ligand-dependent fashion and may participate in ET signal transduction.


* This work was supported by Grants DK52057 and DK56736 from the National Institutes of Health and by a research grant from the American Diabetes Association (to K. V. K.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger Present Address: Parkinson's Inst., Sunnyvale, CA 94089.

§ Present Address: Millennium Pharmaceuticals, Cambridge, MA 02139.

To whom correspondence should be addressed: 715 Albany St., Boston, MA 02118. Tel.: 617-638-5049; Fax: 617-638-5339; E-mail: kandror@biochem.bumc.bu.edu.


Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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