RELB

RELB
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1ZK9, 1ZKA, 2V2T, 3DO7, 3JSS, 3JUZ, 3JV0, 3JV4, 3JV6, 4JGM, 4JHB
Identifiers
Aliases	RELB, I-REL, IREL, REL-B, RELB proto-oncogene, NF-kB subunit, IMD53
External IDs	OMIM: 604758; MGI: 103289; HomoloGene: 4747; GeneCards: RELB; OMA:RELB - orthologs
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19q13.32 Start 45,001,449 bp[1] End 45,038,198 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7 A3|7 9.93 cM Start 19,340,142 bp[2] End 19,363,363 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in granulocyte mucosa of transverse colon cartilage tissue monocyte spleen olfactory zone of nasal mucosa blood upper lobe of left lung stromal cell of endometrium muscle of thigh Top expressed in mesenteric lymph nodes jejunum intestinal villus granulocyte spleen duodenum lactiferous gland colon left colon thymus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding RNA polymerase II transcription regulatory region sequence-specific DNA binding transcription corepressor activity DNA-binding transcription factor activity chromatin binding protein binding protein kinase binding identical protein binding DNA-binding transcription factor activity, RNA polymerase II-specific RNA polymerase II cis-regulatory region sequence-specific DNA binding Cellular component I-kappaB/NF-kappaB complex nucleoplasm microtubule organizing center cytoskeleton nucleus cytoplasm cytosol centrosome protein-containing complex transcription repressor complex Biological process response to cytokine antigen processing and presentation regulation of transcription, DNA-templated rhythmic process regulation of transcription by RNA polymerase II myeloid dendritic cell differentiation stimulatory C-type lectin receptor signaling pathway negative regulation of transcription by RNA polymerase II T-helper 1 cell differentiation negative regulation of interferon-beta production circadian regulation of gene expression transcription, DNA-templated cellular response to osmotic stress positive regulation of gene expression NIK/NF-kappaB signaling T-helper 1 type immune response inflammatory response negative regulation of transcription, DNA-templated I-kappaB kinase/NF-kappaB signaling positive regulation of transcription by RNA polymerase II innate immune response lymphocyte differentiation Sources:Amigo / QuickGO
Orthologs Species Human Mouse 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 Mb Chr 7: 19.34 – 19.36 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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

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

• NF-κB

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

• Taylor JP, Pomerantz R, Bagasra O, Chowdhury M, Rappaport J, Khalili K, Amini S (September 1992). "TAR-independent transactivation by Tat in cells derived from the CNS: a novel mechanism of HIV-1 gene regulation". The EMBO Journal. 11 (9): 3395–403. doi:10.1002/j.1460-2075.1992.tb05418.x. PMC 556874. PMID 1505523.
• Ruben SM, Klement JF, Coleman TA, Maher M, Chen CH, Rosen CA (May 1992). "I-Rel: a novel rel-related protein that inhibits NF-kappa B transcriptional activity". Genes & Development. 6 (5): 745–60. doi:10.1101/gad.6.5.745. PMID 1577270.
• Liu J, Perkins ND, Schmid RM, Nabel GJ (June 1992). "Specific NF-kappa B subunits act in concert with Tat to stimulate human immunodeficiency virus type 1 transcription". Journal of Virology. 66 (6): 3883–7. doi:10.1128/JVI.66.6.3883-3887.1992. PMC 241175. PMID 1583734.
• Biswas DK, Salas TR, Wang F, Ahlers CM, Dezube BJ, Pardee AB (December 1995). "A Tat-induced auto-up-regulatory loop for superactivation of the human immunodeficiency virus type 1 promoter". Journal of Virology. 69 (12): 7437–44. doi:10.1128/JVI.69.12.7437-7444.1995. PMC 189681. PMID 7494249.
• Jeang KT, Chun R, Lin NH, Gatignol A, Glabe CG, Fan H (October 1993). "In vitro and in vivo binding of human immunodeficiency virus type 1 Tat protein and Sp1 transcription factor". Journal of Virology. 67 (10): 6224–33. doi:10.1128/JVI.67.10.6224-6233.1993. PMC 238044. PMID 7690421.
• Alcamí J, Laín de Lera T, Folgueira L, Pedraza MA, Jacqué JM, Bachelerie F, et al. (April 1995). "Absolute dependence on kappa B responsive elements for initiation and Tat-mediated amplification of HIV transcription in blood CD4 T lymphocytes". The EMBO Journal. 14 (7): 1552–60. doi:10.1002/j.1460-2075.1995.tb07141.x. PMC 398242. PMID 7729429.
• Majello B, De Luca P, Hagen G, Suske G, Lania L (November 1994). "Different members of the Sp1 multigene family exert opposite transcriptional regulation of the long terminal repeat of HIV-1". Nucleic Acids Research. 22 (23): 4914–21. doi:10.1093/nar/22.23.4914. PMC 523756. PMID 7800480.
• Taylor JP, Pomerantz RJ, Oakes JW, Khalili K, Amini S (January 1995). "A CNS-enriched factor that binds to NF-kappa B and is required for interaction with HIV-1 tat". Oncogene. 10 (2): 395–400. PMID 7838536.
• Westendorp MO, Shatrov VA, Schulze-Osthoff K, Frank R, Kraft M, Los M, et al. (February 1995). "HIV-1 Tat potentiates TNF-induced NF-kappa B activation and cytotoxicity by altering the cellular redox state". The EMBO Journal. 14 (3): 546–54. doi:10.1002/j.1460-2075.1995.tb07030.x. PMC 398112. PMID 7859743.
• Scala G, Ruocco MR, Ambrosino C, Mallardo M, Giordano V, Baldassarre F, et al. (March 1994). "The expression of the interleukin 6 gene is induced by the human immunodeficiency virus 1 TAT protein". The Journal of Experimental Medicine. 179 (3): 961–71. doi:10.1084/jem.179.3.961. PMC 2191426. PMID 8113688.
• Bours V, Azarenko V, Dejardin E, Siebenlist U (June 1994). "Human RelB (I-Rel) functions as a kappa B site-dependent transactivating member of the family of Rel-related proteins". Oncogene. 9 (6): 1699–702. PMID 8183565.
• Deloukas P, Dauwerse JG, van Ommen GJ, van Loon AP (February 1994). "The human NFKB3 gene encoding the p65 subunit of transcription factor NF-kappa B is located on chromosome 11q12". Genomics. 19 (3): 592–4. doi:10.1006/geno.1994.1115. PMID 8188306.
• Westendorp MO, Li-Weber M, Frank RW, Krammer PH (July 1994). "Human immunodeficiency virus type 1 Tat upregulates interleukin-2 secretion in activated T cells". Journal of Virology. 68 (7): 4177–85. doi:10.1128/JVI.68.7.4177-4185.1994. PMC 236340. PMID 8207793.
• Dobrzanski P, Ryseck RP, Bravo R (March 1993). "Both N- and C-terminal domains of RelB are required for full transactivation: role of the N-terminal leucine zipper-like motif". Molecular and Cellular Biology. 13 (3): 1572–82. doi:10.1128/MCB.13.3.1572. PMC 359469. PMID 8441398.
• Harhaj E, Blaney J, Millhouse S, Sun SC (February 1996). "Differential effects of I kappa B molecules on Tat-mediated transactivation of HIV-1 LTR". Virology. 216 (1): 284–7. doi:10.1006/viro.1996.0062. PMID 8615004.
• Conant K, Ma M, Nath A, Major EO (March 1996). "Extracellular human immunodeficiency virus type 1 Tat protein is associated with an increase in both NF-kappa B binding and protein kinase C activity in primary human astrocytes". Journal of Virology. 70 (3): 1384–9. doi:10.1128/JVI.70.3.1384-1389.1996. PMC 189957. PMID 8627654.
• Demarchi F, d'Adda di Fagagna F, Falaschi A, Giacca M (July 1996). "Activation of transcription factor NF-kappaB by the Tat protein of human immunodeficiency virus type 1". Journal of Virology. 70 (7): 4427–37. doi:10.1128/JVI.70.7.4427-4437.1996. PMC 190376. PMID 8676466.
• Beauparlant P, Kwon H, Clarke M, Lin R, Sonenberg N, Wainberg M, Hiscott J (September 1996). "Transdominant mutants of I kappa B alpha block Tat-tumor necrosis factor synergistic activation of human immunodeficiency virus type 1 gene expression and virus multiplication". Journal of Virology. 70 (9): 5777–85. doi:10.1128/JVI.70.9.5777-5785.1996. PMC 190591. PMID 8709193.
• Ramazzotti E, Vignoli M, Re MC, Furlini G, La Placa M (May 1996). "Enhanced nuclear factor-kappa B activation induced by tumour necrosis factor-alpha in stably tat-transfected cells is associated with the presence of cell-surface-bound Tat protein". AIDS. 10 (5): 455–61. doi:10.1097/00002030-199605000-00002. PMID 8724035. S2CID 84476590.