Activator protein 1 (Fos/Jun) functions in inflammatory bone and skin disease.
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.
Zenz
Rainer
R
Ludwig Boltzmann Institute for Cancer Research, Währinger Strasse 13a, A-1090 Vienna, Austria.
Eferl
Robert
R
Scheinecker
Clemens
C
Redlich
Kurt
K
Smolen
Josef
J
Schonthaler
Helia B
HB
Kenner
Lukas
L
Tschachler
Erwin
E
Wagner
Erwin F
EF
D000818:Animals; D015535:Arthritis, Psoriatic / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000378:metabolism; D001847:Bone Diseases / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004817:Epidermis; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D011565:Psoriasis / Q000378:metabolism; D012871:Skin Diseases / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D016207:Cytokines; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1