FosB

FosB is a member of the Fos family of transcription factors that form the AP-1 complex with Jun proteins to regulate gene expression by binding to AP-1 DNA sites. The FOSB gene is expressed in multiple tissues and is an immediate-early gene activated by stimuli such as growth factors, neuronal activity, stress, and exposure to drugs.

The FOSB gene produces multiple isoforms through alternative splicing and promoter usage, most notably the full-length FosB and a truncated splice variant called deltaFosB. DeltaFosB lacks part of the C-terminus, is unusually stable, and accumulates with repeated or chronic stimuli, leading to prolonged effects on transcription.

In the brain, deltaFosB is enriched in regions associated with reward and motivation, such as the nucleus accumbens and prefrontal cortex, where it acts as a transcription factor to regulate gene networks involved in synaptic remodeling and signaling. These changes are thought to contribute to enduring behavioral adaptations linked to chronic drug exposure and natural rewards. Full-length FosB, by contrast, is more rapidly degraded and participates in immediate adaptive responses to stimuli.

Regulation of FosB activity involves standard AP-1 signaling dynamics, with deltaFosB’s stability distinguishing its effects from those of the transient FosB protein. The persistence of deltaFosB after cessation of stimuli underlies its association with long-lasting changes in neural circuits.

FosB family members are expressed in other tissues beyond the brain as well, and research has explored roles in processes such as bone development and remodeling, illustrating the broader function of AP-1–mediated transcription across tissues.