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. 2023 Feb 20;14:1108915. doi: 10.3389/fphar.2023.1108915

FIGURE 2.

FIGURE 2

(A) Canonical NF-κB pathway. I- Represent binding of TNF-α, Interleukins, Lipopolysaccharides and other cytokines with their specific receptor resulting in activation of TAK kinase-1. II- Activation of TAK-1 result in phosphorylation of IKKΒ unit of the triad consisting of IKKα, IKKβ and IKKγ. III- Phosphorylation of IKKΒ further result in phosphorylation of IκB at Ser19 and Ser23. IV- This phosphorylation allows for ubiquitination and proteasomal degradation of IκB. V- This modification renders NF-κB dimer (p65 and p50) free to translocate to the nucleus. VI- NF-κB dimer (p65 and p50) further binds with specific response elements on DNA and triggers gene transcription of several genes involved in angiogenesis, metastasis, migration and cellular proliferation. (B) Non- canonical NF-κB pathway. I- denotes the binding of TNFR ligands to their respective receptors, which results in the activation of NF-κB inducing kinase-1 (NIK). II- NIK phosphorylates IKKα, causing it to be activated. III- Finally, activated IKKα phosphorylates p100. IV- IKKα mediated phosphorylation of p100 marks it for ubiquitination and proteasomal processing to yield p52. V-p52 forms an active dimer with Rel B and translocates to the nucleus. VI- p52 and Rel B dimer bind to the DNA and cause gene transcription.