RELA
Description
The RELA (RELA proto-oncogene, NF-kB subunit) is a protein-coding gene located on chromosome 11.
Transcription factor p65, also known as nuclear factor NF-kappa-B p65 subunit, is a protein that in humans is encoded by the RELA gene. RELA, also known as p65, is a REL-associated protein involved in NF-κB heterodimer formation, nuclear translocation and activation. NF-κB is an essential transcription factor complex involved in all types of cellular processes, including cellular metabolism, chemotaxis, etc. Phosphorylation and acetylation of RELA are crucial post-translational modifications required for NF-κB activation. RELA has also been shown to modulate immune responses, and activation of RELA is positively associated with multiple types of cancer.
== Gene and expression == RELA, or v-rel avian reticuloendotheliosis viral oncogene homolog A, is also known as p65 or NFKB3. It is located on chromosome 11 q13, and its nucleotide sequence is 1473 nucleotide long. RELA protein has four isoforms, the longest and the predominant one being 551 amino acids. RELA is expressed alongside p50 in various cell types, including epithelial/endothelial cells and neuronal tissues.
== Structure == RELA is one member of the NF-κB family, one of the essential transcription factors under intensive study.
NF-kappa-B is a versatile transcription factor found in nearly all cell types. It acts as the final step in a chain of signaling events triggered by various stimuli linked to processes such as inflammation, immunity, cell development, growth, tumor formation, and programmed cell death. NF-kappa-B is a complex composed of two identical or different proteins from the Rel family: RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL, and NFKB2/p52. The most prevalent combination is the RELA-NFKB1 heterodimer. These dimers bind to specific DNA sequences called kappa-B sites in the genes they regulate, with each dimer showing distinct preferences for different kappa-B sites. Various dimer combinations can either activate or repress gene expression. For instance, RELA-NFKB1 and RELA-REL heterodimers act as activators. NF-kappa-B is regulated by post-translational modifications, subcellular localization, and interactions with other regulatory proteins. Inactive NF-kappa-B complexes reside in the cytoplasm bound to members of the I-kappa-B inhibitor family. In a common activation pathway, I-kappa-B kinases (IKKs) phosphorylate I-kappa-B in response to various activators, leading to I-kappa-B degradation and the release of active NF-kappa-B, which then moves to the nucleus. The primary mechanism of I-kappa-B's inhibitory action on NF-kappa-B is through cytoplasmic retention via interaction with RELA. RELA possesses a weak DNA-binding site, potentially contributing directly to DNA binding within the NF-kappa-B complex. Besides its direct activation role, RELA can also influence the accessibility of promoters to transcription factors, indirectly regulating gene expression. It binds to chromatin at the NF-kappa-B promoter region through association with DDX1. RELA is crucial for cytokine gene expression in T cells (PubMed:15790681). The NF-kappa-B RELA-RELA homodimer appears to be involved in invasin-mediated activation of IL-8 expression. RELA is a key transcription factor regulating the IFN response during SARS-CoV-2 infection (PubMed:33440148).
RELA is also known as AIF3BL3, CMCU, NFKB3, p65.
