Fra1

Fra-1, short for FOS-like antigen 1, is a transcription factor in humans encoded by the FOSL1 gene. It is a member of the FOS family and functions as part of the AP-1 transcription factor complex, which forms when Fra-1 dimerizes with members of the Jun family. This complex binds to DNA at AP-1 sites to regulate gene expression in response to a wide range of stimuli.

Fra-1 is a basic leucine zipper (bZIP) protein whose activity is tightly controlled at the level of expression and protein stability. It is rapidly induced by mitogenic signals such as growth factors and cytokines, often via MAP kinase pathways (including ERK and JNK). Unlike some other transcription factors, Fra-1 is relatively unstable and can be targeted for degradation by the ubiquitin-proteasome system; phosphorylation events can enhance its stability and transcriptional activity.

Functionally, Fra-1 participates in regulating genes involved in cell proliferation, differentiation, survival, migration, and extracellular matrix remodeling. In cancer biology, Fra-1 is frequently upregulated and linked to invasive behavior and metastasis, partly through the induction of matrix metalloproteinases and other matrix-remodeling enzymes, as well as by influencing inflammatory and angiogenic pathways.

In development and physiology, Fra-1 contributes to processes such as placental development and tissue remodeling. Mouse models with altered Fra-1 expression have provided insights into its roles in growth and morphogenesis, as well as in tumor progression. Fra-1 remains a focus of study for understanding AP-1–mediated transcriptional programs and their implications in disease and therapy.