Nuclear factor NF-kappa-B p105 subunit (NFKB1) (NF-κB p50)

The NF-κB p50 homodimer is a transcription factor complex composed of two p50 subunits, which are generated through the limited proteasomal processing of the Nuclear factor NF-kappa-B p105 subunit (NFKB1) precursor protein [1.3.1, 1.3.2]. Unlike the canonical p50/p65 heterodimer, the p50 homodimer lacks a transactivation domain and typically functions as a transcriptional repressor by occupying κB binding sites and recruiting co-repressors such as histone deacetylases (HDACs) [1.3.5, 1.5.1]. However, in certain contexts, it can act as a transcriptional activator when complexed with co-activators like Bcl-3, notably driving the expression of anti-inflammatory cytokines such as IL-10 [1.2.1, 1.3.3]. This dual role makes it a critical regulator of the resolution phase of inflammation and a key player in the development of chronic inflammatory diseases, autoimmune disorders, and various malignancies [1.3.4, 1.5.2]. Therapeutic targeting of the p50 homodimer often involves modulating the NF-κB pathway through proteasome inhibitors like bortezomib, which prevent the processing of p105, or through small molecules and peptides that specifically disrupt its DNA-binding or nuclear translocation [1.4.2, 1.4.3].

Other names

NFKB1p50p105KBF1EBP-1Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1

Inhibition of p105 processing, inhibition of DNA binding, and inhibition of nuclear translocation [1.4.2, 1.4.3]