RELB

Transcription factor RelB is a protein that in humans is encoded by the RELB gene.[5]

RELB
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesRELB, I-REL, IREL, REL-B, RELB proto-oncogene, NF-kB subunit, IMD53
External IDsOMIM: 604758 MGI: 103289 HomoloGene: 4747 GeneCards: RELB
Orthologs
SpeciesHumanMouse
Entrez

5971

19698

Ensembl

ENSG00000104856

ENSMUSG00000002983

UniProt

Q01201

Q04863

RefSeq (mRNA)

NM_006509

NM_001290457
NM_009046

RefSeq (protein)

NP_006500

NP_001277386
NP_033072

Location (UCSC)Chr 19: 45 – 45.04 MbChr 7: 19.34 – 19.36 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Interactions

RELB has been shown to interact with NFKB2,[6][7] NFKB1,[6] and C22orf25.[8]

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,[9] 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.[10] 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.

Most intriguingly, a recent study identified that TNF-induced canonical signalling subverts non-canonical RelB:p52 activity in the inflamed lymphoid tissues limiting lymphocyte ingress.[11] Mechanistically, TNF inactivated NIK in LTβR‐stimulated cells and induced the synthesis of Nfkb2 mRNA encoding p100; these together potently accumulated unprocessed p100, which attenuated the RelB activity. A role of p100/Nfkb2 in dictating lymphocyte ingress in the inflamed lymphoid tissue may have broad physiological implications.

See also

References

  1. GRCh38: Ensembl release 89: ENSG00000104856 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000002983 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Bours V, Burd PR, Brown K, Villalobos J, Park S, Ryseck RP, et al. (February 1992). "A novel mitogen-inducible gene product related to p50/p105-NF-kappa B participates in transactivation through a kappa B site". Molecular and Cellular Biology. 12 (2): 685–95. doi:10.1128/MCB.12.2.685. PMC 364259. PMID 1531086.
  6. Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, et al. (February 2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nature Cell Biology. 6 (2): 97–105. doi:10.1038/ncb1086. PMID 14743216. S2CID 11683986.
  7. Thornburg NJ, Pathmanathan R, Raab-Traub N (December 2003). "Activation of nuclear factor-kappaB p50 homodimer/Bcl-3 complexes in nasopharyngeal carcinoma". Cancer Research. 63 (23): 8293–301. PMID 14678988.
  8. "Molecular Interaction Database". Archived from the original on 2006-05-06.
  9. Bonizzi G, Bebien M, Otero DC, Johnson-Vroom KE, Cao Y, Vu D, et al. (October 2004). "Activation of IKKalpha target genes depends on recognition of specific kappaB binding sites by RelB:p52 dimers". The EMBO Journal. 23 (21): 4202–10. doi:10.1038/sj.emboj.7600391. PMC 524385. PMID 15470505.
  10. Basak S, Shih VF, Hoffmann A (May 2008). "Generation and activation of multiple dimeric transcription factors within the NF-kappaB signaling system". Molecular and Cellular Biology. 28 (10): 3139–50. doi:10.1128/MCB.01469-07. PMC 2423155. PMID 18299388.
  11. Mukherjee T, Chatterjee B, Dhar A, Bais SS, Chawla M, Roy P, et al. (December 2017). "A TNF-p100 pathway subverts noncanonical NF-κB signaling in inflamed secondary lymphoid organs". The EMBO Journal. 36 (23): 3501–3516. doi:10.15252/embj.201796919. PMC 5709727. PMID 29061763.

Further reading

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