Biology:RELB

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Transcription factor RelB is a protein that in humans is encoded by the RELB gene.[1]

Interactions

RELB has been shown to interact with NFKB2,[2][3] NFKB1,[2] and C22orf25.[4]

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,[5] 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.[6] 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.[7] 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. ↑ "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. February 1992. doi:10.1128/MCB.12.2.685. PMID 1531086. 
  2. ↑ 2.0 2.1 "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nature Cell Biology 6 (2): 97–105. February 2004. doi:10.1038/ncb1086. PMID 14743216. 
  3. ↑ "Activation of nuclear factor-kappaB p50 homodimer/Bcl-3 complexes in nasopharyngeal carcinoma". Cancer Research 63 (23): 8293–301. December 2003. PMID 14678988. 
  4. ↑ "Molecular Interaction Database". http://mint.bio.uniroma2.it/mint/Welcome.do. 
  5. ↑ "Activation of IKKalpha target genes depends on recognition of specific kappaB binding sites by RelB:p52 dimers". The EMBO Journal 23 (21): 4202–10. October 2004. doi:10.1038/sj.emboj.7600391. PMID 15470505. 
  6. ↑ "Generation and activation of multiple dimeric transcription factors within the NF-kappaB signaling system". Molecular and Cellular Biology 28 (10): 3139–50. May 2008. doi:10.1128/MCB.01469-07. PMID 18299388. 
  7. ↑ "A TNF-p100 pathway subverts noncanonical NF-κB signaling in inflamed secondary lymphoid organs". The EMBO Journal 36 (23): 3501–3516. December 2017. doi:10.15252/embj.201796919. PMID 29061763. 

Further reading



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