NFkB p65

RELA (v-rel reticuloendotheliosis viral oncogene homolog A), also known as Nuclear factor NFkB p65 subunit, or Transcription factor p65, is a transcription factor expressed in growth plate chondrocytes where it facilitates chondrogenesis. The v-rel avian reticuloendotheliosis viral oncogene homolog A (RELA) gene encodes the major component of the NF-?B complex. NFkB p65B is a generic name for an evolutionarily conserved transcription-factor system that contributes to the mounting of an effective immune response but is also involved in the regulation of cell proliferation, development, and apoptosis. The implication of NFkB p65 in central biological processes and its extraordinary connectivity to other signaling pathways raise a need for highly controlled regulation of NFkB p65 activity at several levels.

NFkB p65 Related Areas

 

NFkB p65 Related Pathways

• EGFR Signaling Pathway

NFkB p65 Alternative Names

RELA, MGC131774, NFKB3, p65 [Homo sapiens]

Rela, p65 [Mus musculus]

Summaries for NFkB p65

Entrez Gene summary for RELA:

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 RELA gene.

OMIM - description for NFkB p65:

NFKB1 (164011) or NFKB2 (164012) is bound to REL (164910), RELA, or RELB (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, 164008 or NFKBIB, 604495), which inactivate NFKB by trapping it in the cytoplasm. Phosphorylation of serine residues on the I-kappa-B proteins by kinases (IKBKA, 600664, or IKBKB, 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 such as 5-prime GGGRNNYYCC 3-prime or 5-prime HGGARNYYCC 3-prime (where H is A, C, or T; R is an A or G purine; and Y is a C or T pyrimidine).

Human NFkB p65 Protein General Information

 

• Protein names: Nuclear factor NF-kappa-B p65 subunit, Short Name=NFkB p65
• Sequence length: 551 AA.
• Domain: the 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.
• Sequence similarities: Contains 1 RHD (Rel-like) domain.
• Post-translational modification: Ubiquitinated, leading to its proteasomal degradation. Degradation is required for termination of NFkB p65 response. Ref.30 Monomethylated at Lys-310 by SETD6. Monomethylation at Lys-310 is recognized by the ANK repeats of EHMT1 and promotes the formation of repressed chromatin at target genes, leading to down-regulation of NFkB p65 transcription factor activity. Phosphorylation at Ser-311 disrupts the interaction with EHMT1 without preventing monomethylation at Lys-310 and relieves the repression of target genes
• Subunit structure: omponent of the NFkB p65-p50 complex. Component of the NFkB p65-c-Rel complex. Homodimer; component of the NFkB p65-p65 complex. Component of the NFkB p65-p52 complex. May interact with ETHE1. Binds AES and TLE1. Interacts with TP53BP2. Binds to and is phosphorylated by the activated form of either RPS6KA4 or RPS6KA5. Interacts with ING4 and this interaction may be indirect. Interacts with CARM1, USP48 and UNC5CL. Interacts with IRAK1BP1
• Subcellular location: Nucleus. Cytoplasm. Note: Colocalized with DDX1 in the nucleus upon TNF-alpha induction By similarity. Nuclear, but also found in the cytoplasm in an inactive form complexed to an inhibitor (I-kappa-B). Colocalizes with GFI1 in the nucleus after LPS stimulation.

General information above from UniProt

Function for NFkB p65 Protein

UniProtKB:

NFKB is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NFKB is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52 and the heterodimeric p65-p50 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. NF-kappa-B heterodimeric p65-p50 and p65-c-Rel complexes are transcriptional activators. The NF-kappa-B p65-p65 complex appears to be involved in invasin-mediated activation of IL-8 expression. The inhibitory effect of I-kappa-B upon NF-kappa-B the cytoplasm is exerted primarily through the interaction with p65. p65 shows a weak DNA-binding site which could contribute directly to DNA binding in the NF-kappa-B complex. Associates with chromatin at the NF-kappa-B promoter region via association with DDX1.

Genatlas:

• NFkB p65 is nuclear transcription factor of kappa light chain enhancer in B cells
• NFkB p65 regulates inducible transcription of a large number of genes in response to diverse stimuli (Pubmed 18215660)
• NFkB p65 is critical regulator of T-cell survival by affecting the balance of BCL2 family members (Pubmed 18034190)
• acetylated form of NFkB p65 coactivates transcriptional activation of NF-KappaB through binding to BRD4 (Pubmed 19103749)
• RELA-mediated regulation of BECN1 could be important for T-cell activation and proliferation, highlighting a novel mechanism whereby NFkB p65 could promote cell survival (Pubmed 19289499)
• NFkB p65 regulates BECN1 transcription, probably due to its ability to directly act on the BECN1 promoter (Pubmed 19289499)
• NFkB p65 can positively regulate constitutive autophagy, possibly due to its ability to regulate BECN1 expression (Pubmed 19289499)
• NFkB p65 represses CTNNB1-activated transcription of cyclin D1 (Pubmed 21056029)