FOSB
Description
The FOSB (FosB proto-oncogene, AP-1 transcription factor subunit) is a protein-coding gene located on chromosome 19.
Protein fosB, also known as FosB and G0/G1 switch regulatory protein 3 (G0S3), is a protein that in humans is encoded by the FBJ murine osteosarcoma viral oncogene homolog B (FOSB) gene. The FOS gene family consists of four 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, although Δ2ΔFosB lacks a known transactivation domain, in turn preventing it from affecting transcription through the AP-1 complex. The ΔFosB splice variant has been identified as playing a central, crucial role in the development and maintenance of addiction. ΔFosB overexpression (i.e., an abnormally and excessively high level of ΔFosB expression which produces a pronounced gene-related phenotype) triggers the development of addiction-related neuroplasticity throughout the reward system and produces a behavioral phenotype that is characteristic of an addiction. 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.
== DeltaFosB == DeltaFosB – more commonly written as ΔFosB – is a truncated splice variant of the FOSB gene. ΔFosB has been implicated as a critical factor in the development of virtually all forms of behavioral and drug addictions.
FOSB protein forms a complex with JUN family proteins to create the AP-1 transcription factor. This complex binds to specific DNA sequences (AP-1 consensus sequence) to activate gene expression. FOSB, as part of AP-1, works with other cell-specific factors to regulate gene expression by binding to enhancers and recruiting the SWI/SNF (BAF) chromatin remodeling complex to make DNA accessible. Together with JUN, FOSB is involved in T cell death by activating the expression of FASLG/CD95L, a gene crucial for this process. FOSB exhibits transcriptional activity in vitro and is linked to nurturing behavior in newborns. FOSB may be important for neurogenesis in the hippocampus and is involved in learning and memory processes by regulating genes related to these functions. It has also been implicated in morphine reward and spatial memory. FOSB interacts with several other proteins, including SMARCB1, SMARCD1, ARID1A, and JUN. It can exist as a monomer under reducing conditions or as a dimer under oxidizing conditions. FOSB may regulate neurogenesis in the hippocampus and play a role in synaptic modifications in the brain, potentially contributing to addiction.
FOSB is also known as AP-1, G0S3, GOS3, GOSB.
Associated Diseases
- juvenile myoclonic epilepsy
- intellectual disability, autosomal dominant 10
- benign familial infantile epilepsy
- epilepsy, progressive myoclonic, 12
- febrile seizures, familial, 1
- Potocki-Lupski syndrome
