Fra1

FosB is a protein that in humans is encoded by the FOSB gene. FosB is a member of the Fos gene family, which includes c-Fos, FosB, Fra-1, and Fra-2. These proteins are transcription factors that form heterodimers with Jun proteins to create the activator protein-1 (AP-1) complex, which regulates gene expression in response to a variety of stimuli, including growth factors, cytokines, and stress.

Structure

FosB, like other members of the Fos family, contains a basic leucine zipper (bZIP) domain, which is responsible for DNA binding and dimerization with Jun proteins. The bZIP domain is characterized by a region rich in basic amino acids followed by a leucine zipper motif, which facilitates the formation of stable dimers.

Function

FosB plays a critical role in the regulation of cell proliferation, differentiation, and survival. It is involved in the cellular response to extracellular signals and is implicated in various biological processes, including the immune response, bone development, and neuronal activity.

Role in the Brain

In the central nervous system, FosB is rapidly induced in response to neural activity and is associated with synaptic plasticity, learning, and memory. A truncated splice variant of FosB, known as ΔFosB, accumulates in the brain following repeated exposure to drugs of abuse and is thought to play a role in the development of addiction. ΔFosB is more stable than the full-length protein and can persist in neurons for extended periods, leading to long-lasting changes in gene expression and behavior.

Clinical Significance

Alterations in FosB expression have been linked to various pathological conditions. Overexpression of FosB has been observed in certain types of cancer, where it may contribute to tumor progression and metastasis. In the context of psychiatric disorders, changes in FosB and ΔFosB levels have been associated with depression, schizophrenia, and bipolar disorder.

Research Applications

FosB is often used as a marker of neuronal activation in neuroscience research. Its expression can be measured to assess the activity of specific brain regions in response to various stimuli, such as stress, drugs, or learning tasks.

Also see

• c-Fos
• Jun proteins
• Activator protein-1
• ΔFosB
• Transcription factor