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MALT Lymphoma : Non-Canonical NF-κB Pathway

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Non-canonical activation of NF-κB causes slow but sustained transcriptional responses. This pathway is regulated by NF-κB inducible kinase (NIK) which, in resting cells, is degraded by E3 ligase complex (consisting of TRAF2/TRAF3 adaptor proteins and E3 ligases BIRC2/3).

Non-canonical pathway begin with activation of one of the TNFR family receptors (CD40, BAFFR, or APRIL) which inactivates E3 ligase complex and stabilizes NIK. Increased NIK levels promote IKKα phosphorylation which leads to phosphorylation of RelB/p100, partial proteasomal digestion of p100, and release of RelB/p52 dimers that translocate to the nucleus and regulate gene expression.

Image source: Schreuder MI et al. Novel developments in the pathogenesis and diagnosis of extranodal marginal zone lymphoma. J Hematop. 2017 Dec. 10(3-4): 91-107. Cropped from the original and used under Creative Commons Attribution 4.0 International License.

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