deltaFosB

DeltaFosB is a truncated splice variant of the FosB gene that encodes a transcription factor belonging to the Fos family of the activator protein-1 (AP-1) complex. Unlike the full-length FosB, DeltaFosB lacks a C-terminal degron, which makes the protein unusually stable and capable of accumulating in targeted brain regions with repeated stimulation.

DeltaFosB forms functional AP-1 transcription factor complexes by dimerizing with Jun family proteins and binding to AP-1 sites in target gene promoters. Through recruitment of coactivators and chromatin remodeling enzymes, DeltaFosB modulates histone acetylation and the expression of downstream genes involved in synaptic plasticity, neuronal structure, and signaling.

In the mammalian brain, DeltaFosB accumulates in reward-related regions such as the nucleus accumbens and, to a lesser extent, the dorsal striatum and prefrontal cortex, in response to chronic exposure to drugs of abuse (e.g., cocaine, amphetamine, nicotine, alcohol) as well as natural rewards (e.g., sugar, physical activity). The protein tends to persist for weeks after withdrawal, contributing to long-lasting changes in neural circuits.

Functionally, DeltaFosB is viewed as a molecular switch that enhances sensitivity to drugs and stresses experience, promoting long-lasting behavioral and structural plasticity. Animal studies link DeltaFosB induction to addictive behaviors and, in some contexts, to responses related to mood and stress regulation. Because of its stability and region-specific effects, DeltaFosB remains a central focus in research on the molecular basis of addictive and reward-related behaviors.