V-Rel Reticuloendotheliosis Viral Oncogene Homolog A (RELA)

NFKB3; p65; REL-A; Nuclear Factor Of Kappa Light Polypeptide Gene Enhancer In B-Cells 3; Transcription Factor P65; Nuclear factor NF-kappa-B p65 subunit

SPN	W194
HGNC	9955
MGI	103290
PubMed	16135789
RGD	727889
UniProt	Q04206
Wiki	RELA

The transcriptional coactivator CBP/p300 associates with through 2 sites, an N-terminal domain that interacts with the C-terminal region of unphosphorylated p65, and a second domain that only interacts with p65 phosphorylated on serine-276. Phosphorylation by PKA both weakens the interaction between the N- and C-terminal regions of p65 and creates an additional site for interaction with CBP/p300. Therefore, PKA regulates the transcriptional activity of NF-kappa-B by modulating its interaction with CBP/p300.

The p50 (NFKB1)/p65 (RELA) heterodimer is the most abundant form of NFKB. The NFKB complex is inhibited by I-kappa-B proteins (NFKBIA or NFKBIB ), which inactivate NFKB by trapping it in the cytoplasm.

Reference

"Isolation of a rel-related human cDNA that potentially encodes the 65-kD subunit of NF-kappa B."
Science 251:1490-1493(1991) [PubMed] [Europe PMC] [Abstract]

"Genomic organization of the gene encoding the p65 subunit of NF-kappa B: multiple variants of the p65 protein may be generated by alternative splicing."
Hum. Mol. Genet. 2:1895-1900(1993) [PubMed] [Europe PMC] [Abstract]

"An alternatively spliced transcript, p65 delta 2, of the gene encoding the p65 subunit of the transcription factor NF-kappa B."
Gene 138:265-266(1994) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Functional characterization of the NF-kappa B p65 transcriptional activator and an alternatively spliced derivative."
Mol. Cell. Biol. 12:444-454(1992) [PubMed] [Europe PMC] [Abstract]

"A novel complex between the p65 subunit of NF-kappa B and c-Rel binds to a DNA element involved in the phorbol ester induction of the human urokinase gene."
EMBO J. 11:205-213(1992) [PubMed] [Europe PMC] [Abstract]

"I kappa B/MAD-3 masks the nuclear localization signal of NF-kappa B p65 and requires the transactivation domain to inhibit NF-kappa B p65 DNA binding."
Mol. Biol. Cell 3:1339-1352(1992) [PubMed] [Europe PMC] [Abstract]

"Activation of multiple NF-kappa B/Rel DNA-binding complexes by tumor necrosis factor."
Oncogene 9:1487-1492(1994) [PubMed] [Europe PMC] [Abstract]

"Regulation of intercellular adhesion molecule-1 gene by tumor necrosis factor-alpha is mediated by the nuclear factor-kappaB heterodimers p65/p65 and p65/c-Rel in the absence of p50."
Cell Growth Differ. 8:335-342(1997) [PubMed] [Europe PMC] [Abstract]

"A new member of the IkappaB protein family, IkappaB epsilon, inhibits RelA (p65)-mediated NF-kappaB transcription."
Mol. Cell. Biol. 17:6184-6190(1997) [PubMed] [Europe PMC] [Abstract]

"IKAP is a scaffold protein of the IkappaB kinase complex."
Nature 395:292-296(1998) [PubMed] [Europe PMC] [Abstract]

"IkappaB kinases phosphorylate NF-kappaB p65 subunit on serine 536 in the transactivation domain."
J. Biol. Chem. 274:30353-30356(1999) [PubMed] [Europe PMC] [Abstract]

"NF-kappaB subunit p65 binds to 53BP2 and inhibits cell death induced by 53BP2."
Oncogene 18:5177-5186(1999) [PubMed] [Europe PMC] [Abstract]

"Yersinia enterocolitica invasin protein triggers IL-8 production in epithelial cells via activation of Rel p65-p65 homodimers."
FASEB J. 14:1471-1484(2000) [PubMed] [Europe PMC] [Abstract]

"Inhibition of nuclear factor-kappaB-mediated transcription by association with the amino-terminal enhancer of split, a Groucho-related protein lacking WD40 repeats."
J. Biol. Chem. 275:4383-4390(2000) [PubMed] [Europe PMC] [Abstract]

"Tumor necrosis factor alpha-induced phosphorylation of RelA/p65 on Ser529 is controlled by casein kinase II."
J. Biol. Chem. 275:32592-32597(2000) [PubMed] [Europe PMC] [Abstract]

"The tumor suppressor protein menin interacts with NF-kappaB proteins and inhibits NF-kappaB-mediated transactivation."
Oncogene 20:4917-4925(2001) [PubMed] [Europe PMC] [Abstract]

"Duration of nuclear NF-kappaB action regulated by reversible acetylation."
Science 293:1653-1657(2001) [PubMed] [Europe PMC] [Abstract]

"A novel protein overexpressed in hepatoma accelerates export of NF-kappa B from the nucleus and inhibits p53-dependent apoptosis."
Cancer Cell 2:335-346(2002) [PubMed] [Europe PMC] [Abstract]

"Acetylation of RelA at discrete sites regulates distinct nuclear functions of NF-kappaB."
EMBO J. 21:6539-6548(2002) [PubMed] [Europe PMC] [Abstract]

"The phosphorylation status of nuclear NF-kappa B determines its association with CBP/p300 or HDAC-1."
Mol. Cell 9:625-636(2002) [PubMed] [Europe PMC] [Abstract]

"Transcriptional activation of the NF-kappaB p65 subunit by mitogen- and stress-activated protein kinase-1 (MSK1)."
EMBO J. 22:1313-1324(2003) [PubMed] [Europe PMC] [Abstract]

"Post-activation turn-off of NF-kappa B-dependent transcription is regulated by acetylation of p65."
J. Biol. Chem. 278:2758-2766(2003) [PubMed] [Europe PMC] [Abstract]

"RING finger protein AO7 supports NF-kappaB-mediated transcription by interacting with the transactivation domain of the p65 subunit."
J. Biol. Chem. 278:26879-26887(2003) [PubMed] [Europe PMC] [Abstract]

"Glycogen synthase kinase-3 beta regulates NF-kappa B1/p105 stability."
J. Biol. Chem. 278:39583-39590(2003) [PubMed] [Europe PMC] [Abstract]

"Regulation of NF-kappaB signaling by Pin1-dependent prolyl isomerization and ubiquitin-mediated proteolysis of p65/RelA."
Mol. Cell 12:1413-1426(2003) [PubMed] [Europe PMC] [Abstract]

"Identification of a ZU5 and death domain-containing inhibitor of NF-kappaB."
J. Biol. Chem. 279:17819-17825(2004) [PubMed] [Europe PMC] [Abstract]

"Suppression of MEK/ERK signaling pathway enhances cisplatin-induced NF-kappaB activation by protein phosphatase 4-mediated NF-kappaB p65 Thr dephosphorylation."
J. Biol. Chem. 279:26143-26148(2004) [PubMed] [Europe PMC] [Abstract]

"Degradation of promoter-bound p65/RelA is essential for the prompt termination of the nuclear factor kappaB response."
J. Exp. Med. 200:107-113(2004) [PubMed] [Europe PMC] [Abstract]

"Identification of beta-arrestin2 as a G protein-coupled receptor-stimulated regulator of NF-kappaB pathways."
Mol. Cell 14:303-317(2004) [PubMed] [Europe PMC] [Abstract]

"The candidate tumour suppressor protein ING4 regulates brain tumour growth and angiogenesis."
Nature 428:328-332(2004) [PubMed] [Europe PMC] [Abstract]

"Regulation of NF-kappaB and p53 through activation of ATR and Chk1 by the ARF tumour suppressor."
EMBO J. 24:1157-1169(2005) [PubMed] [Europe PMC] [Abstract]

"IKKbeta phosphorylates p65 at S468 in transactivation domain 2."
FASEB J. 19:1758-1760(2005) [PubMed] [Europe PMC] [Abstract]

"cis-acting, element-specific transcriptional activity of differentially phosphorylated nuclear factor-kappa B."
J. Biol. Chem. 280:244-252(2005) [PubMed] [Europe PMC] [Abstract]

"COMMD proteins, a novel family of structural and functional homologs of MURR1."
J. Biol. Chem. 280:22222-22232(2005) [PubMed] [Europe PMC] [Abstract]

"NF-kappaB RelA phosphorylation regulates RelA acetylation."
Mol. Cell. Biol. 25:7966-7975(2005) [PubMed] [Europe PMC] [Abstract]

"Foxp3 interacts with nuclear factor of activated T cells and NF-kappa B to repress cytokine gene expression and effector functions of T helper cells."
Proc. Natl. Acad. Sci. U.S.A. 102:5138-5143(2005) [PubMed] [Europe PMC] [Abstract]

"Respiratory syncytial virus M2-1 protein induces the activation of nuclear factor kappa B."
Virology 331:260-268(2005) [PubMed] [Europe PMC] [Abstract]

"Activation of the nuclear factor kappaB pathway by astrocyte elevated gene-1: implications for tumor progression and metastasis."
Cancer Res. 66:1509-1516(2006) [PubMed] [Europe PMC] [Abstract]

"Human ubiquitin specific protease 31 is a deubiquitinating enzyme implicated in activation of nuclear factor-kappaB."
Cell. Signal. 18:83-92(2006) [PubMed] [Europe PMC] [Abstract]

"Inducible phosphorylation of NF-kappa B p65 at serine 468 by T cell costimulation is mediated by IKK epsilon."
J. Biol. Chem. 281:6175-6183(2006) [PubMed] [Europe PMC] [Abstract]

"Breast cancer metastasis suppressor 1 functions as a corepressor by enhancing histone deacetylase 1-mediated deacetylation of RelA/p65 and promoting apoptosis."
Mol. Cell. Biol. 26:8683-8696(2006) [PubMed] [Europe PMC] [Abstract]

"Coactivator-associated arginine methyltransferase-1 enhances nuclear factor-kappaB-mediated gene transcription through methylation of histone H3 at arginine 17."
Mol. Endocrinol. 20:1562-1573(2006) [PubMed] [Europe PMC] [Abstract]

"IL-1 receptor-associated kinase 1 is critical for latent membrane protein 1-induced p65/RelA serine 536 phosphorylation and NF-kappaB activation."
Proc. Natl. Acad. Sci. U.S.A. 103:2689-2694(2006) [PubMed] [Europe PMC] [Abstract]

"Nine-amino-acid transactivation domain: establishment and prediction utilities."
Genomics 89:756-768(2007) [PubMed] [Europe PMC] [Abstract]

"UXT is a novel and essential cofactor in the NF-kappaB transcriptional enhanceosome."
J. Cell Biol. 178:231-244(2007) [PubMed] [Europe PMC] [Abstract]

"The familial Mediterranean fever protein, pyrin, is cleaved by caspase-1 and activates NF-kappaB through its N-terminal fragment."
Blood 112:1794-1803(2008) [PubMed] [Europe PMC] [Abstract]

"Functional characterization of the atopy-associated gene PHF11."
J. Allergy Clin. Immunol. 121:1148-1154(2008) [PubMed] [Europe PMC] [Abstract]

"AKIP1 enhances NF-kappaB-dependent gene expression by promoting the nuclear retention and phosphorylation of p65."
J. Biol. Chem. 283:7834-7843(2008) [PubMed] [Europe PMC] [Abstract]

"The DEAD-box RNA helicase DDX1 interacts with RelA and enhances nuclear factor kappaB-mediated transcription."
J. Cell. Biochem. 106:296-305(2009) [PubMed] [Europe PMC] [Abstract]

"Brd4 coactivates transcriptional activation of NF-kappaB via specific binding to acetylated RelA."
Mol. Cell. Biol. 29:1375-1387(2009) [PubMed] [Europe PMC] [Abstract]

"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]

"A novel LZAP-binding protein, NLBP, inhibits cell invasion."
J. Biol. Chem. 285:12232-12240(2010) [PubMed] [Europe PMC] [Abstract]

"SIRT2 regulates NF-kappaB dependent gene expression through deacetylation of p65 Lys310."
J. Cell Sci. 123:4251-4258(2010) [PubMed] [Europe PMC] [Abstract]

"Zinc finger protein Gfi1 controls the endotoxin-mediated Toll-like receptor inflammatory response by antagonizing NF-kappaB p65."
Mol. Cell. Biol. 30:3929-3942(2010) [PubMed] [Europe PMC] [Abstract]

"Initial characterization of the human central proteome."
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]

"NF-kappaB repression by PIAS3 mediated RelA SUMOylation."
PLoS ONE 7:E37636-E37636(2012) [PubMed] [Europe PMC] [Abstract]

"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]

"C11orf95-RELA fusions drive oncogenic NF-kappaB signalling in ependymoma."
Nature 506:451-455(2014) [PubMed] [Europe PMC] [Abstract]

"Structure of an IkappaBalpha/NF-kappaB complex."
Cell 95:749-758(1998) [PubMed] [Europe PMC] [Abstract]