NFKB2p52

NFKB2p52 refers to the p52 protein, the mature product of the NF-κB2 gene. The NFKB2 gene encodes a precursor protein called p100, which is processed proteolytically to produce p52. The p100/p52 family is part of the NF-κB transcription factor system, with p52 primarily functioning as a component that forms active dimers in conjunction with RelB.

In terms of structure and activity, p52 retains the Rel homology domain needed for DNA binding and dimerization but lacks a typical transactivation domain. The p52–RelB dimer binds κB sites in target gene promoters to regulate transcription. p100 contains ankyrin repeats that inhibit NF-κB activity by cytoplasmic retention; upon processing, these inhibitory elements are removed, allowing p52 to participate in gene regulation.

Processing of p100 to p52 occurs mainly through the noncanonical NF-κB signaling pathway. Activation is driven by certain members of the tumor necrosis factor receptor superfamily, including BAFF receptor, CD40, and lymphotoxin β receptor. These signals stabilize NIK (MAP3K14), which activates IKKα. IKKα-mediated phosphorylation and partial proteolysis of p100 release p52, which then translocates to the nucleus to drive transcription in cooperation with RelB.

Biological roles of p52/RelB include the development and function of secondary lymphoid organs and the maturation and function of B cells, as well as the regulation of genes involved in immune responses, such as chemokines and chemokine receptors.

Clinical significance: Mutations in NFKB2 can cause immunodeficiency with CVID-like features, sometimes accompanied by adrenal insufficiency, reflecting the importance of the noncanonical NF-κB pathway in immune and endocrine homeostasis.