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Highly Accessed Review

Activator protein 1 (Fos/Jun) functions in inflammatory bone and skin disease

Rainer Zenz12, Robert Eferl12, Clemens Scheinecker3, Kurt Redlich3, Josef Smolen3, Helia B Schonthaler4, Lukas Kenner125, Erwin Tschachler6 and Erwin F Wagner47*

Author affiliations

1 Ludwig Boltzmann Institute for Cancer Research, Währinger Strasse 13a, A-1090 Vienna, Austria

2 Center for Biomolecular Medicine and Pharmacy, Medical University of Vienna, Währinger Strasse 13a, A-1090 Vienna, Austria

3 Division of Rheumatology, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria

4 Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, A-1030 Vienna, Austria

5 Clinical Institute of Pathology, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria

6 Department of Dermatology, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria

7 Cancer Cell Biology Program, Spanish National Cancer Center (CNIO), Melchor Fernandez Almagro 3, E-28029 Madrid, Spain

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Citation and License

Arthritis Research & Therapy 2008, 10:201  doi:10.1186/ar2338

Published: 18 January 2008

Abstract

Activator protein 1 (AP-1) (Fos/Jun) is a transcriptional regulator composed of members of the Fos and Jun families of DNA binding proteins. The functions of AP-1 were initially studied in mouse development as well as in the whole organism through conventional transgenic approaches, but also by gene targeting using knockout strategies. The importance of AP-1 proteins in disease pathways including the inflammatory response became fully apparent through conditional mutagenesis in mice, in particular when employing gene inactivation in a tissue-specific and inducible fashion. Besides the well-documented roles of Fos and Jun proteins in oncogenesis, where these genes can function both as tumor promoters or tumor suppressors, AP-1 proteins are being recognized as regulators of bone and immune cells, a research area termed osteoimmunology. In the present article, we review recent data regarding the functions of AP-1 as a regulator of cytokine expression and an important modulator in inflammatory diseases such as rheumatoid arthritis, psoriasis and psoriatic arthritis. These new data provide a better molecular understanding of disease pathways and should pave the road for the discovery of new targets for therapeutic applications.