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

J. Biol. Chem., Vol. 280, Issue 7, 5154-5162, February 18, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/7/5154    most recent M411575200v1 Alert me when this article is cited 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, H. Articles by Danielpour, D. Search for Related Content PubMed PubMed Citation Articles by Wang, H. Articles by Danielpour, D. Social Bookmarking                      What's this?

Novel Function of Androgen Receptor-associated Protein 55/Hic-5 as a Negative Regulator of Smad3 Signaling^*

Hui Wang, Kyung Song, Tracy L. Sponseller, and David Danielpour

From the Ireland Cancer Center Research Laboratories and Department of Pharmacology, Case Western Reserve University/University Hospitals, Cleveland, Ohio 44106

Androgen receptor-associated protein 55 (ARA55/Hic-5) belongs to the LIM protein superfamily and is featured by three or four N-terminal LD motifs and four C-terminal zinc finger-like LIM domains. Both LD motifs and LIM domains can serve as protein-protein interaction interfaces. Recently, we found that enforced expression of ARA55 inhibits transforming growth factor--mediated up-regulation of Smad binding element-luciferase reporter activity in NRP-154 and NRP-152 rat prostate and LNCaP human prostate cell lines. Moreover, ARA55 also inhibits the induction of Smad-binding element 4-luciferase and 3TP-luciferase (a plasminogen activator inhibitor-1 (PAI-1) promoter construct) reporters by constitutively active (CA)-Smad3 in these cell lines. Co-immunoprecipitation studies suggest an interaction between ARA55 and either CA-Smad3 or wild-type Smad3 in HEK293 cells that occurs through the MH2 domain of Smad3 and the C terminus of ARA55 with wild-type Smad3 having stronger affinity than CA-Smad3 to ARA55. Glutathione S-transferase pull-down assays demonstrate that this interaction can occur in a cell-free system. These results are consistent with the luciferase data showing that the C terminus of ARA55 is critical for suppression of Smad3 activity. Furthermore, using a mammalian two-hybrid system, we confirmed that ARA55 interacts with the MH2 domain of Smad3 and suppresses CA-Smad3-induced transcriptional responses. In conclusion, these results support that ARA55 selectively intercepts transforming growth factor- signaling through an interaction of the LIM domain of ARA55 with the MH2 domain of Smad3.

Received for publication, October 12, 2004

^* This work was supported by NCI Grants 1R01CA102074 and 1R01CA092102 from the National Institutes of Health. 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.

To whom correspondence should be addressed: Case Comprehensive Cancer Center, Case Western Reserve University, Wolstein Research Bldg., Rm. 3532, 2103 Cornell Rd., Cleveland, OH 44106. Tel.: 216-368-5670; Fax: 216-368-8919; E-mail: david.danielpour{at}case.edu.

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

This article has been cited by other articles:

				Y. H. Lee, U. S. Kayyali, A. M. Sousa, T. Rajan, R. J. Lechleider, and R. M. Day Transforming Growth Factor-beta1 Effects on Endothelial Monolayer Permeability Involve Focal Adhesion Kinase/Src Am. J. Respir. Cell Mol. Biol., October 1, 2007; 37(4): 485 - 493. [Abstract] [Full Text] [PDF]

				S. Lu, J. Lee, M. Revelo, X. Wang, S. Lu, and Z. Dong Smad3 Is Overexpressed in Advanced Human Prostate Cancer and Necessary for Progressive Growth of Prostate Cancer Cells in Nude Mice Clin. Cancer Res., October 1, 2007; 13(19): 5692 - 5702. [Abstract] [Full Text] [PDF]

				K. Mori, M. Asakawa, M. Hayashi, M. Imura, T. Ohki, E. Hirao, J.-r. Kim-Kaneyama, K. Nose, and M. Shibanuma Oligomerizing Potential of a Focal Adhesion LIM Protein Hic-5 Organizing a Nuclear-Cytoplasmic Shuttling Complex J. Biol. Chem., August 4, 2006; 281(31): 22048 - 22061. [Abstract] [Full Text] [PDF]

				S. M. Ghogomu, S. van Venrooy, M. Ritthaler, D. Wedlich, and D. Gradl HIC-5 Is a Novel Repressor of Lymphoid Enhancer Factor/T-cell Factor-driven Transcription J. Biol. Chem., January 20, 2006; 281(3): 1755 - 1764. [Abstract] [Full Text] [PDF]