HISTOLOGY AND HISTOPATHOLOGY

Cellular and Molecular Biology

 

Review

The transcription factor Fos: a Janus-type regulator in health and disease

Moritz Durchdewald, Peter Angel and Jochen Hess

German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, Division of Signal Transduction and Growth Control, Heidelberg, Germany.

Offprint requests to: Peter Angel, German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, Division of Signal Transduction and Growth Control (A100), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. e-mail: p.angel@dkfz.de


Summary. The immediate early gene product Fos is part of the activator protein-1 (AP-1) transcription factor and has been shown to participate in the molecular mechanisms of cell proliferation, differentiation, apoptosis, and transformation. The analysis of genetically modified mice and cells derived thereof has provided important new insights into its specific biological functions in development, tissue homeostasis, and cellular responses to environmental insults. Moreover, the deregulation of Fos could be linked with a variety of pathological conditions, including immunological, skeletal and neurological defects, as well as oncogenic transformation and tumor progression. In contrast to the mainstream opinion concerning the oncogenic function of Fos an increasing number of experimental reports also describe a tumor-suppressive function in various cancer types. More recently, altered Fos expression in cell culture and mouse models combined with global gene expression analysis unraveled novel downstream effectors of the Fos-regulated genetic program. Finally, selective inhibition of its function with a small molecule inhibitor in a preclinical mouse model of arthritis demonstrated that targeting Fos/AP-1 activity could be an auspicious new option for clinical use
. Histol Histopathol 24, 1451-1461 (2009)

Key words: AP-1, Bone, Cancer, CNS, Oncogene

DOI: 10.14670/HH-24.1451