FOSB

FBJ murine osteosarcoma viral oncogene homolog B, also known as FOSB or FosB, is a protein that, in humans, is encoded by the FOSB gene.

The FOS gene family consists of 4 members: FOS, FOSB, FOSL1, and FOSL2. These genes encode leucine zipper proteins that can dimerize with proteins of the JUN family (e.g., c-Jun, JunD), thereby forming the transcription factor complex AP-1. As such, the FOS proteins have been implicated as regulators of cell proliferation, differentiation, and transformation. FosB and its truncated splice variants ΔFosB and (further truncated) Δ2ΔFosB are all involved in osteosclerosis, even though Δ2ΔFosB lacks a known transactivation domain, preventing it from affecting gene transcription through the AP-1 complex.

The ΔFosB splice variant has been identified as playing a central, crucial (necessary and sufficient) role in the development and maintenance of pathological behavior and neural plasticity involved in both behavioral addictions (associated with natural rewards) and drug addictions. For example, ΔFosB overexpression triggers the development of addiction-related structural neuroplasticity throughout the reward system. ΔFosB differs from the full length FosB and further truncated Δ2ΔFosB in its capacity to produce these effects, as only accumbal ΔFosB overexpression is associated with pathological responses to drugs.