NFKB1

Nuclear factor NF-kappa-B p105 subunit is a protein that in humans is encoded by the NFKB1 gene.

This gene encodes a 105 kD protein which can undergo cotranslational processing by the 26S proteasome to produce a 50 kD protein. The 105 kD protein is a Rel protein-specific transcription inhibitor and the 50 kD protein is a DNA binding subunit of the NF-kappaB (NF-κB) protein complex. NF-κB is a transcription factor that is activated by various intra- and extra-cellular stimuli such as cytokines, oxidant-free radicals, ultraviolet irradiation, and bacterial or viral products. Activated NF-κB translocates into the nucleus and stimulates the expression of genes involved in a wide variety of biological functions; over 200 known genes are targets of NF-κB in various cell types, under specific conditions. Inappropriate activation of NF-κB has been associated with a number of inflammatory diseases while persistent inhibition of NF-κB leads to inappropriate immune cell development or delayed cell growth.

Model organisms

Nfkb1 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Normal
Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Abnormal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Abnormal
Plasma immunoglobulins	Abnormal
Haematology	Abnormal
Peripheral blood lymphocytes	Abnormal
Micronucleus test	Normal
Heart weight	Normal
Tail epidermis wholemount	Normal
Skin Histopathology	Normal
Brain histopathology	Normal
Salmonella infection	Abnormal
All tests and analysis from

Model organisms have been used in the study of NFKB1 function. A conditional knockout mouse line, called Nfkb1^{tm1a(KOMP)Wtsi} was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty five tests were carried out on mutant mice and six significant abnormalities were observed. Female homozygotes had a decreased respiratory quotient, increased circulating alkaline phosphatase level and increased leukocyte cell number. Male homozygotes showed an increased susceptibility to Salmonella infection, while homozygotes of both sex had decreased IgG1 and decreased regulatory T cell and NK cell numbers.

Interactions

NFKB1 has been shown to interact with:

• BCL3,
• C22orf25,
• HDAC1,
• HMGA2
• IKK2,
• ITGB3BP,
• IκBα,
• LYL1,
• MAP3K7IP2,
• MAP3K8,
• MEN1,
• NFKB2,
• NFKBIE,
• NOTCH1,
• Nuclear receptor coactivator 1,
• RELA,
• RELB,
• STAT3,
• STAT6, and
• TSC22D3.

External links

• NFKB1 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
• FactorBook NFKB

This article incorporates text from the United States National Library of Medicine, which is in the public domain.