NFKB1 (OMIM 164011) or NFKB2 (OMIM 164012) is bound to REL (OMIM 164910), RELA, or RELB (OMIM 604758) to form the NFKB complex.
The p50 (NFKB1)/p65 (RELA) heterodimer is the most abundant form of NFKB. The NFKB complex is inhibited by
I-kappa-B proteins (NFKBIA, OMIM 164008 or NFKBIB, OMIM 604495), which inactivate NFKB by trapping it in the cytoplasm.
Phosphorylation of serine residues on the I-kappa-B proteins by kinases (IKBKA, OMIM 600664, or IKBKB, OMIM 603258) marks them
for destruction via the ubiquitination pathway, thereby allowing activation of the NFKB complex. Activated NFKB complex
translocates into the nucleus and binds DNA at kappa-B-binding motifs.
NCBI Summary:
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-kappa-B (NFKB) protein complex. NFKB is a transcription regulator that is activated by various intra- and extra-cellular stimuli such as cytokines, oxidant-free radicals, ultraviolet irradiation, and bacterial or viral products. Activated NFKB translocates into the nucleus and stimulates the expression of genes involved in a wide variety of biological functions. Inappropriate activation of NFKB has been associated with a number of inflammatory diseases while persistent inhibition of NFKB leads to inappropriate immune cell development or delayed cell growth. Alternative splicing results in multiple transcript variants encoding different isoforms, at least one of which is proteolytically processed. [provided by RefSeq, Feb 2016]
Role of nuclear factor-κB pathway in the transition of mouse secondary follicles to antral follicles. Xu JJ et al. (2019) Nuclear factor-κB (NF-κB) signaling is involved in regulating a great number of normal and abnormal cellular events. However, little is known about its role in ovarian follicular development. In this study, we found NF-κB signaling is activated during the transition from secondary to antral follicles. We generated active NF-κB mice and found that antral follicular numbers were higher than wild-type ovaries. Activation of NF-κB signaling could enhance granulosa cell proliferation and regress granulosa cell apoptosis of mouse ovarian follicles. Higher follicle-stimulating hormone receptor (FSHR) and luteinizing hormone/choriogonadotropin receptor expressions were observed in active NF-κB ovaries compared to wild type. Furthermore, we confirmed that NF-κB signaling was indeed involved in the granulosa cell viability and proliferation through FSHR using COV434 cell line. This is the first experimental evidence that NF-κB signaling is implicated in the control of follicular development through FSHR and its corresponding target molecules, which might be achieved by targeting proliferation and apoptosis in follicular granulosa cells.//////////////////
Expression regulated by
Comment
Ovarian localization
Granulosa
Comment
Wang YF, et al 2002 reported the involvement of inhibitory nuclear factor-kappa B (NF kappaB)-independent NF kappa B activation in the gonadotropic regulation of X-linked inhibitor of apoptosis expression during
ovarian follicular development in vitro.
Increased X-linked inhibitor of apoptosis (XIAP) expression and suppressed
follicular apoptosis are important determinants in the regulation of
follicular development by FSH. FSH (100 ng/ml) increased rat granulosa cell XIAP mRNA abundance and
protein content. The gonadotropin also induced granulosa cell p65
subunit-containing NFkappaB translocation from cytoplasm to nucleus and
increased NFkappaB-DNA binding activity. Supershift EMSA indicated the
FSH-activated NFkappaB contained p65 and p50 subunits. Unlike TNFalpha, FSH
failed to elicit a significant change in granulosa cell phospho- and
total-inhibitory NFkappaB (IkappaB) IkappaB contents in vitro and
dominant-negative IkappaB expression was ineffective in blocking the increase
in NFkappaB-DNA-binding activity and XIAP protein content induced by the
gonadotropin. In contrast, SN50 (a cell permeable inhibitory peptide of
NFkappaB translocation, 50-200 ng/ml) suppressed FSH-stimulated NFkappaB-DNA
binding, XIAP expression, and follicular growth. FSH also increased granulosa
cell phospho-Akt contents, a response sensitive to the PI-3K inhibitor
LY294002 (10 mum). In conclusion, the present studies demonstrate that the
FSH-induced XIAP expression is mediated through the NFkappaB pathway through
activation of phosphatidylinositol 3-kinase rather than the classical IkappaB
kinase.