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:
NF-kappa-B is a ubiquitous transcription factor involved in several biological processes. It is held in the cytoplasm in an inactive state by specific inhibitors. Upon degradation of the inhibitor, NF-kappa-B moves to the nucleus and activates transcription of specific genes. NF-kappa-B is composed of NFKB1 or NFKB2 bound to either REL, RELA, or RELB. The most abundant form of NF-kappa-B is NFKB1 complexed with the product of this gene, RELA. Four transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]
General function
DNA binding
Comment
Cellular localization
Cytoplasmic, Nuclear
Comment
Ovarian function
Follicle atresia, Steroid metabolism
Comment
Inhibition of NF-κB promotes autophagy via JNK signaling pathway in porcine granulosa cells. Gao H et al. (2016) The transcription factor nuclear factor-κB (NF-κB) plays an important role in diverse processes, including cell proliferation and differentiation, apoptosis and inflammation. However, the role of NF-κB in porcine follicle development is not clearly elucidated. In this study, we demonstrated that follicle stimulating hormone (FSH) increased the level of inhibitor of NF-κB (IκB) protein and promoted the cytoplasmic localization of p65, indicating that FSH inhibits the activation of NF-κB in porcine granulosa cells. Moreover, inhibition of NF-κB by FSH or another specific inhibitor of NF-κB, pyrrolidine dithiocarbamate (PDTC), could activate JNK signaling and enhance autophagic activity in porcine granulosa cells. Knockdown of RelA (p65) Subunit of NF-κB by RNA interference abrogated the activation of JNK signaling pathway and the increase of autophagic protein expression by FSH. Meanwhile, the functional significance of FSH or PDTC-mediated autophagy were further investigated. Our results demonstrated that the increased autophagy promoted progesterone secretion in porcine granulosa cells. Blockage of autophagy by chloroquine obviated the FSH or PDTC-induced progesterone production. Taken together, these results indicate that inhibition of NF-κB increased autophagy via JNK signaling, and promote steroidogenesis in porcine granulosa cells. Our results provide new insights into the regulation and function of autophagy in mammalian follicle development.//////////////////
Expression regulated by
FSH
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.