NF-κB1/p50

NF-κB1/p50 is generated from the NFKB1 product through 26S proteasome-dependent cotranslational processing and forms DNA-binding NF-κB dimers, including the prototypical p50:RelA/p65 complex^[1][2]. Mechanistically, p50 supports inflammatory-response control because p50 homodimers activate IL-10 transcription in macrophages and p50-deficient macrophages show decreased IL-10 with increased TNF and IL-12 after LPS stimulation^[3]. In chronic liver injury models, loss of nfkb1 causes more severe neutrophilic inflammation and fibrosis, linking p50 to restraint of TNF-α-driven tissue damage^[4]. Compared with RelA/p65, RelB, and c-Rel, p50 lacks a transactivation domain, so p50:p50 complexes often function through cofactors rather than direct transcriptional activation^[2]. In activated hepatic stellate cells, the p50:p50:HDAC1 complex represses Ccl2, Cxcl10, Gm-csf, and Mmp-13, defining a disease-relevant anti-inflammatory NF-κB1/p50 mechanism^[5]. For experimental applications, BCL-3-p50 biology provides a modifiable axis because a BCL-3-mimetic peptide was designed from the ANK1 region that interacts with p50^[6].