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

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: fj.07-104604v1 fj.07-104604v2 22/9/3337    most recent Alert me when this article is cited Alert me if a correction is posted 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 Google Scholar Articles by Fauquier, L. Articles by Vandel, L. PubMed PubMed Citation Articles by Fauquier, L. Articles by Vandel, L.

Dual role of the arginine methyltransferase CARM1 in the regulation of c-Fos target genes

Lucas Fauquier^*, Carine Duboé^*, Cécile Joré^*, Didier Trouche and Laurence Vandel^*,1

^* Université de Toulouse, Centre de Biologie du Développement, UMR 5547, CNRS, IFR109, Toulouse, France; and

Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération, UMR 5088, Toulouse, France.

¹ Correspondence: Centre de Biologie du Développement, UMR 5547 CNRS/Université Paul Sabatier, 118 route de Narbonne, F-31062 Toulouse, France. E-mail: vandel{at}cict.fr

Fos proteins, the prototypic members of basic region-leucine zipper (bZIP) transcription factors, bind to other bZIP proteins to form the activator protein-1 (AP-1) complex, which regulates the expression of a plethora of target genes. Notably, c-Fos target genes include members of the matrix metalloproteinase (MMP) gene family and c-fos is overexpressed in a number of metastatic cancers, suggesting its direct involvement in this process. Here, we reveal that c-Fos-mediated transcriptional activation is regulated by the protein arginine methyltransferase CARM1 and by all three members of the p160 protein family of coactivators. Carm1-deficient cells showed a dramatic reduction in the expression level of c-Fos target genes MMP-1b, -3, and -13, indicating a major role for CARM1 in regulating the expression of these genes. RNA interference combined with quantitative polymerase chain reaction demonstrated that CARM1 and p160 proteins synergize to activate expression of MMP-1b, -3, and -13 in vivo. Furthermore, we show that CARM1 also regulates MMP expression at the post-transcriptional level, either positively or negatively. Our data indicate that CARM1 can play a dual role in the expression of AP-1 target genes involved in cancer or other diseases by acting at the transcriptional as well as at the post-transcriptional levels.—Fauquier, L., Duboé, C., Joré, C., Trouche, D., Vandel, L. Dual role of the arginine methyltransferase CARM1 in the regulation of c-Fos target genes.

Key Words: p160 proteins • MMPs • AP-1 • transcription • mRNA stability • post-transcriptional regulation