RELB
Description
The RELB (RELB proto-oncogene, NF-kB subunit) is a protein-coding gene located on chromosome 19.
Transcription factor RelB is a protein that in humans is encoded by the RELB gene.
== Interactions == RELB has been shown to interact with NFKB2, NFKB1, and C22orf25.
== Activation and function == In resting cells, RelB is sequestered by the NF-κB precursor protein p100 in the cytoplasm. A select set of TNF-R superfamily members, including lymphotoxin β-receptor (LTβR), BAFF-R, CD40 and RANK, activate the non-canonical NF-κB pathway. In this pathway, NIK stimulates the processing of p100 into p52, which in association with RelB appears in the nucleus as RelB:p52 NF-κB heterodimers. RelB:p52 activates the expression homeostatic lymphokines, which instruct lymphoid organogenesis and determine the trafficking of naive lymphocytes in the secondary lymphoid organs. Recent studies has suggested that the functional non-canonical NF-κB pathway is modulated by canonical NF-κB signalling. For example, syntheses of the constituents of the non-canonical pathway, viz RelB and p52, are controlled by canonical IKK2-IκB-RelA:p50 signalling. Moreover, generation of canonical and non-canonical dimers, viz RelA:p50 and RelB:p52, within the cellular milieu are mechanistically interlinked. These analyses suggest that an integrated NF-κB system network underlies activation of both RelA and RelB containing dimer and that a malfunctioning canonical pathway will lead to an aberrant cellular response also through the non-canonical pathway.
NF-kappa-B is a crucial transcription factor found in virtually all cell types, playing a vital role in diverse biological processes including inflammation, immunity, cell differentiation, growth, tumor development, and programmed cell death (apoptosis). It exists as a homo- or heterodimeric complex assembled from proteins containing the Rel-like domain: RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL, and NFKB2/p52. These dimers bind to kappa-B sites within the DNA of their target genes, displaying distinct preferences and binding affinities for different kappa-B sites. The specific dimer combinations act as either transcriptional activators or repressors. NF-kappa-B's activity is tightly regulated through mechanisms involving post-translational modifications, subcellular localization, and interactions with cofactors or corepressors. NF-kappa-B complexes are maintained in an inactive state in the cytoplasm, bound to members of the NF-kappa-B inhibitor (I-kappa-B) family. Upon activation by various stimuli, I-kappa-B undergoes phosphorylation by I-kappa-B kinases (IKKs), leading to its degradation and the release of the active NF-kappa-B complex, which translocates to the nucleus. Heterodimeric complexes of RelB-p50 and RelB-p52 function as transcriptional activators. Notably, RELB does not directly associate with DNA or with RELA/p65 or REL. It enhances promoter activity in the presence of NFKB2/p49. As a member of the NUPR1/RELB/IER3 survival pathway, RELB potentially confers significant resistance to cell stress, such as starvation or gemcitabine treatment, in pancreatic ductal adenocarcinoma. It regulates the circadian clock by suppressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer, independent of CRY1/CRY2. This repression is heightened in the presence of NFKB2/p52. RELB is essential for both T and B lymphocyte maturation and function. {ECO:0000269|PubMed:1732739, ECO:0000269|PubMed:22565310, ECO:0000269|PubMed:26385063, ECO:0000269|PubMed:7925301, ECO:0000269|PubMed:8441398}
RELB is also known as I-REL, IMD53, IREL, REL-B.
