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

J. Biol. Chem., Vol. 281, Issue 31, 21582-21587, August 4, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/31/21582    most recent M602312200v2 M602312200v1 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 Nijman, S. M. B. Articles by Bernards, R. Search for Related Content PubMed PubMed Citation Articles by Nijman, S. M. B. Articles by Bernards, R. Social Bookmarking                      What's this?

A Functional Genetic Screen Identifies TFE3 as a Gene That Confers Resistance to the Anti-proliferative Effects of the Retinoblastoma Protein and Transforming Growth Factor-^*

Sebastian M. B. Nijman, E. Marielle Hijmans, Selma El Messaoudi, Miranda M. W. van Dongen, Claude Sardet, and René Bernards¹

From the Division of Molecular Carcinogenesis and Centre for Biomedical Genetics, The Netherlands Cancer Institute, 121 Plesmanlaan, 1066 CX Amsterdam, The Netherlands and Institut de Genetique Moleculaire, Unité Mixte de Recherche 5535/IFR24 CNRS, 1919 Route de Mende 34293, Montpellier Cedex 5, France

The helix-loop-helix transcription factor TFE3 has been suggested to play a role in the control of cell growth by acting as a binding partner of transcriptional regulators such as E2F3, SMAD3, and LEF-1 (1–4). Furthermore, translocations/TFE3 fusions have been directly implicated in tumorigenesis (5–7). Surprisingly, however, a direct functional role for TFE3 in the regulation of proliferation has not been reported. By screening retroviral cDNA expression libraries to identify cDNAs that confer resistance to a pRB-induced proliferation arrest, we have found that TFE3 overrides a growth arrest in Rat1 cells induced by pRB and its upstream regulator p16^INK4A. In addition, TFE3 expression blocks the anti-mitogenic effects of TGF- in rodent and human cells. We provide data supporting a role for endogenous TFE3 in the direct regulation of CYCLIN E expression in an E2F3-dependent manner. These observations establish TFE3 as a functional regulator of proliferation and offer a potential mechanism for its involvement in cancer.

Received for publication, March 13, 2006 , and in revised form, May 30, 2006.

^* This work was supported by grants from The Netherlands Organization of Scientific Research, the Human Frontiers Science Program, and La Ligue Nationale Contre Le Cancer. 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. Tel.: 31-20-512-1952; Fax: 31-20-512-1954; E-mail: r.bernards{at}nki.nl.

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

This article has been cited by other articles:

				M. Tsuda, I. J. Davis, P. Argani, N. Shukla, G. G. McGill, M. Nagai, T. Saito, M. Lae, D. E. Fisher, and M. Ladanyi TFE3 Fusions Activate MET Signaling by Transcriptional Up-regulation, Defining Another Class of Tumors as Candidates for Therapeutic MET Inhibition Cancer Res., February 1, 2007; 67(3): 919 - 929. [Abstract] [Full Text] [PDF]