p105

p105, also known as NF-κB1 p105, is a human protein that serves as the precursor of the NF-κB p50 subunit. It is encoded by the NFKB1 gene and has an approximate molecular weight of 105 kilodaltons. The p105/p50 system is a central component of the NF-κB transcription factor family, which regulates immune and inflammatory responses. The p105 protein contains an N-terminal Rel homology domain required for DNA binding and dimerization, and a C-terminal region composed of ankyrin repeats that imposes an inhibitory constraint on NF-κB activity.

p105 exists in the cytoplasm in complex with Rel family members and IκB-like proteins, where it can act as an inhibitor by sequestering NF-κB dimers. Upon stimulation, proteasomal processing of p105 C-terminus generates the mature p50 subunit, which lacks the transactivation domain and participates in the formation of active NF-κB transcription factor dimers, often with RelA (p65) or other Rel proteins. This processing is tightly regulated by signaling cascades, including those that activate the IKK complex.

Functionally, p105 contributes to NF-κB signaling both as a precursor to p50 and as a regulator of NF-κB activity. p50-containing dimers regulate a wide range of genes involved in immune responses, cell survival, and inflammation. The p105/p50 axis thus plays a critical role in normal immunity; dysregulation, mutation, or haploinsufficiency of NFKB1 can lead to immunodeficiency, autoimmune disorders, or cancer.

In humans, NFKB1 is located on chromosome 4 (4q24). Abnormalities in NFKB1/p105 have been linked to common variable immunodeficiency and other disorders, highlighting its importance in health and disease.