RELA

GeneName

RELA

Summary

RELA, also known as Rel or transcription factor p65, is a 60kDa protein that functions as a transcription factor and is a key component of the NF-kappaB signaling pathway. It is predominantly expressed in the nucleus and cytoplasm, where it plays a crucial role in regulating gene expression in response to various stimuli, including cytokines and stress signals. RELA is involved in chromatin organisation and can bind to DNA as a transcription activator or repressor, influencing processes such as inflammation, immune responses, and cellular defence mechanisms. It is associated with several cellular components, including the NF-kappaB complex and transcription regulator complexes, and is implicated in various biological processes such as organ morphogenesis, antiviral responses, and the regulation of apoptotic pathways.

Importance

RELA is relevant to: - The study of inflammatory diseases due to its role in cytokine-mediated signalling and the regulation of inflammatory responses. - Cancer research, as it is involved in the regulation of genes associated with cell proliferation and survival. - Understanding immune responses, particularly in the context of viral infections and autoimmune diseases, given its role in the antiviral innate immune response. - Neurobiology, as it participates in signalling pathways that affect neuronal development and function.

Top Products

For researchers investigating RELA, we recommend two excellent primary antibodies that cater to a variety of applications. The first is the highly regarded polyclonal antibody, Anti-NF-kB p65 antibody (ab16502), which has garnered an impressive 1501 citations, underscoring its reliability in the field. This antibody is validated for use in Western blotting (WB), immunohistochemistry (IHC), immunocytochemistry (ICC), and immunoprecipitation (IP), making it a versatile choice for your research needs. Additionally, we offer the recombinant monoclonal antibody, Anti-NF-kB p65 antibody [E379] (ab32536). This product has also been validated in knockout models and is suitable for the same applications as the polyclonal antibody, including WB, IHC, ICC, and IP. With 714 citations, it is well-established in the research community and provides the batch-to-batch consistency that is often essential for reproducible results. Together, these antibodies provide robust options for studying RELA effectively. The Anti-NF-kB p65 antibody ELISA Kit (ab32536) is an excellent option for researchers looking to measure RELA, with an impressive 714 citations supporting its reliability and effectiveness.

Abcam Product Citation Summary

The data indicates a significant focus on the RELA target in various biological contexts, particularly in studies related to inflammation, NF-κB signaling, and cellular responses to different treatments. The use of Abcam antibodies in both human and animal models highlights the relevance of RELA in understanding disease mechanisms and therapeutic responses.

Abcam Product Citation Table

Domain

The transcriptional activation domain 3/TA3 does not participate in the direct transcriptional activity of RELA but is involved in the control by RELA of the accessibility of target gene promoters. Mediates interaction with ZBTB7A.

The transcriptional activation domain 1/TA1 and the transcriptional activation domain 2/TA2 have direct transcriptional activation properties (By similarity). The 9aaTAD motif found within the transcriptional activation domain 2 is a conserved motif present in a large number of transcription factors that is required for their transcriptional transactivation activity (PubMed:17467953).

Function

NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B 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. The heterodimeric RELA-NFKB1 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. The NF-kappa-B heterodimeric RELA-NFKB1 and RELA-REL complexes, for instance, function as transcriptional activators. 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. The inhibitory effect of I-kappa-B on NF-kappa-B through retention in the cytoplasm is exerted primarily through the interaction with RELA. RELA shows a weak DNA-binding site which could contribute directly to DNA binding in the NF-kappa-B complex. Beside its activity as a direct transcriptional activator, it is also able to modulate promoters accessibility to transcription factors and thereby indirectly regulate gene expression. Associates with chromatin at the NF-kappa-B promoter region via association with DDX1. Essential for cytokine gene expression in T-cells (PubMed:15790681). The NF-kappa-B homodimeric RELA-RELA complex appears to be involved in invasin-mediated activation of IL-8 expression. Key transcription factor regulating the IFN response during SARS-CoV-2 infection (PubMed:33440148).

Involvement in disease

A chromosomal aberration involving ZFTA is found in more than two-thirds of supratentorial ependymomas. Translocation with ZFTA produces a ZFTA-RELA fusion protein. ZFTA-RELA translocations are potent oncogenes that probably transform neural stem cells by driving an aberrant NF-kappa-B transcription program (PubMed:24553141).

Autoinflammatory disease, familial, Behcet-like 3

AIFBL3

An autosomal dominant, mucocutaneous disease characterized by chronic mucosal lesions, in absence of recurrent infections.

None

The disease may be caused by variants affecting the gene represented in this entry.

Post-translational modifications

Ubiquitinated by RNF182, leading to its proteasomal degradation (PubMed:31432514). Degradation is required for termination of NF-kappa-B response. Polyubiquitinated via 'Lys-29'-linked ubiquitin; leading to lysosomal degradation (PubMed:21518757).

Monomethylated at Lys-310 by SETD6 (PubMed:21515635). 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 NF-kappa-B 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 (By similarity).

Phosphorylation at Ser-311 disrupts the interaction with EHMT1 and promotes transcription factor activity (By similarity). Phosphorylation on Ser-536 stimulates acetylation on Lys-310 and interaction with CBP; the phosphorylated and acetylated forms show enhanced transcriptional activity. Phosphorylation at Ser-276 by RPS6KA4 and RPS6KA5 promotes its transactivation and transcriptional activities.

Phosphorylation at Ser-75 by herpes simplex virus 1/HHV-1 inhibits NF-kappa-B activation.

Reversibly acetylated; the acetylation seems to be mediated by CBP, the deacetylation by HDAC3 and SIRT2. Acetylation at Lys-122 enhances DNA binding and impairs association with NFKBIA. Acetylation at Lys-310 is required for full transcriptional activity in the absence of effects on DNA binding and NFKBIA association. Acetylation at Lys-310 promotes interaction with BRD4. Acetylation can also lower DNA-binding and results in nuclear export. Interaction with BRMS1 promotes deacetylation of Lys-310. Lys-310 is deacetylated by SIRT2.

S-nitrosylation of Cys-38 inactivates the enzyme activity.

Sulfhydration at Cys-38 mediates the anti-apoptotic activity by promoting the interaction with RPS3 and activating the transcription factor activity.

Sumoylation by PIAS3 negatively regulates DNA-bound activated NF-kappa-B.

Proteolytically cleaved within a conserved N-terminus region required for base-specific contact with DNA in a CPEN1-mediated manner, and hence inhibits NF-kappa-B transcriptional activity (PubMed:18212740).

Cellular localization

• Nucleus
• Cytoplasm
• Nuclear, but also found in the cytoplasm in an inactive form complexed to an inhibitor (I-kappa-B) (PubMed:1493333). Colocalized with DDX1 in the nucleus upon TNF-alpha induction (PubMed:19058135). Colocalizes with GFI1 in the nucleus after LPS stimulation (PubMed:20547752). Translocation to the nucleus is impaired in L.monocytogenes infection (PubMed:20855622).

Alternative names

NFKB3, RELA, Transcription factor p65, Nuclear factor NF-kappa-B p65 subunit, Nuclear factor of kappa light polypeptide gene enhancer in B-cells 3

Database links

swissprot:Q04206 omim:164014 entrezGene:5970

Other research areas

• Epigenetics
• Immuno-oncology