NFKB2

NFKB2 (Nuclear Factor Kappa B Subunit 2) is a protein that plays a critical role in the immune system and in the regulation of inflammation. It is part of the NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) family, which is involved in cellular responses to stimuli such as stress, cytokines, free radicals, ultraviolet irradiation, oxidized LDL, and bacterial or viral antigens. NFKB2 is encoded by the NFKB2 gene in humans.

Function

NFKB2 is a key component of the NF-κB signaling pathway. NF-κB is a transcription factor that is involved in the regulation of genes that control cell proliferation, survival, and differentiation. It plays a significant role in the immune response to infection. NFKB2, along with other NF-κB subunits, is activated by various intra- and extracellular signals. Once activated, it translocates to the nucleus where it binds to κB sites in the DNA and regulates the transcription of target genes.

Structure

The NFKB2 protein is characterized by a Rel homology domain (RHD) at its N-terminus, which is responsible for DNA binding, dimerization, and interaction with inhibitors of NF-κB, known as IκBs. The C-terminus of NFKB2 contains a series of ankyrin repeats that are involved in protein-protein interactions.

Pathway

The activation of NFKB2 involves its liberation from IκB proteins in the cytoplasm. This process is typically initiated by signaling pathways that lead to the phosphorylation and subsequent degradation of IκBs, allowing NFKB2 to enter the nucleus. In the nucleus, NFKB2 binds to specific DNA sequences and regulates the expression of genes involved in immune and inflammatory responses, cell adhesion, protection against apoptosis, and cell growth.

Clinical Significance

Alterations in the NFKB2 gene or dysregulation of the NF-κB pathway can lead to a variety of diseases, including inflammatory and autoimmune diseases, viral infections, and cancer. Mutations in the NFKB2 gene have been associated with common variable immunodeficiency (CVID), a disorder characterized by impaired B cell differentiation and antibody production.

Research

Research into NFKB2 and the NF-κB pathway continues to be a significant area of study, with the aim of understanding the complex roles these proteins play in health and disease. This research holds the potential for the development of new therapeutic strategies targeting NF-κB signaling in various diseases.

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