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The nuclear factor kappa B (NF-κB) transcriptionfactor coordinates several aspects of innate and adaptiveimmunity, inflammation, cell survival and proliferation [1,2]. Dysregulation of the NF-κB pathway has been associ-ated with cancer development and progression as well aswith other human diseases including viral infections anda number of inflammatory diseases [1]. NF-κB is formedthrough the dimerization of 5 subunits, including membersof the Rel protein family, namely RelA (p65), c-Rel, RelB,NF-κB1 (p50 and its precursor p105) and NF-κB2 (p52and its precursor p 100). Two pathways are involved in theactivation of NF-κB. In both these pathways, kinase activityand proteasome activity play a major role in freeing NF-κBfrom cytoplasmic inhibitors to promote its nuclear translo-cation and activation. The classical or canonical pathwayis activated by a large range of stimuli (microbial and viralinfections, proinflammatory cytokines). In this pathway,NF-κB dimers, mostly p50/RelA and p50/c-Rel, are usuallyretained in the cytoplasm by their interaction with specificinhibitors, called IκBs. Stimuli activate NF-κB through IκBkinase (IKK)-dependent phosphorylation (the IKK complexis composed of 2 kinase subunits, IKKα and IKKβ and a
The nuclear factor kappa B (NF-κB) transcription factor coordinates several aspects of innate and adaptive immunity, inflammation, cell survival and proliferation [1,2]. Dysregulation of the NF-κB pathway has been associated-ated with cancer development and progression as well NF-κB is formed through the dimerization of 5 subunits, including members of the Rel protein family, respectively RelA (p65), c-Rel, RelB, NF-κB1 ( p50 and its precursor p105) and NF-κB2 (p52 and its precursor p 100). Two pathways are involved in the activation of NF-κB. In both these pathways, kinase activity and proteasome activity play a major role in freeing NF-κB from cytoplasmic inhibitors to promote its nuclear translocation and activation. The classical or canonical pathway is activated by a large range of stimuli (microbial and viral infections, proinflammatory cytokines). In this pathway, NF-kB dimers, mostly p50 / RelA and p50 / c-Rel, are usuallyretained in the cytoplasm by their interaction with specific inhibitors, called IκBs. Stimuli activate NF-κB through IκBkinase (IKK) -dependent phosphorylation (the IKK complexis composed of 2 kinase subunits, IKKα and IKKβ and a