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

Rainer Zenz,Erwin Tschachler,Robert Eferl,Clemens Scheinecker,Kurt Redlich,Helia B Schonthaler,Lukas Kenner,Josef Smolen,Erwin F Wagner

doi:10.1186/ar2338

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.

Highlights

The transcription factor activator protein 1 (AP-1) consists of dimers composed of members of the Jun, Fos and activating transcription factor protein families
It was somewhat surprising that gene knockout experiments demonstrated rather tissue-specific and cellspecific functions of individual AP-1 components, in development. Some of these specific functions from conditional AP-1 knockout studies are implicated in diseases that are linked to inflammatory processes such as rheumatoid arthritis (RA) or psoriasis
The latter possibility is convincingly demonstrated in the psoriasis-like mouse model with deletions of JunB and Jun in epidermal cells

Summary

Introduction

The transcription factor activator protein 1 (AP-1) consists of dimers composed of members of the Jun, Fos and activating transcription factor protein families. Many important insights regarding the specific functions of AP-1 proteins in development and disease have been obtained from genetically modified mice and the cells derived thereof (Table 1) [1,2]. Conditional knockout and gain of function (transgenic) approaches applied to study the role of Jun and Fos proteins during development and in diseases.

Results

Conclusion