期刊
CHEMBIOCHEM
卷 5, 期 10, 页码 1348-1358出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.200400144
关键词
cytokines; gene expression; NF-kappa B; signal transduction; transactivation
NF-kappaB is a generic name for an evolutionarily conserved transcription-factor system that contributes to the mounting of an effective immune response buts also involved in the regulation of cell proliferation; development and apoptosis. The implication of NF-kappaB in central biological processes and its extraordinary connectivity to other signaling pathways raise a need for highly controlled regulation of NF-kappaB activity at several levels. While all NF-kappaB activation pathways share a central and critical proteasome-mediated step that leads to the degradation of inhibitory proteins and the release of DNA-binding subunits, there is evidence for a downstream level of NF-kappaB regulation that employs several mechanisms. These include promoter-specific exchange of dimers and modification of the transactivating p65 subunit by phosphorylation, acetylation, ubiquitination, or prolyl isomerization. The signaling pathways and enzymes controlling this second level of regulation and their potential use as therapeutic targets for the treatment of NF-kappaB-associated pathologies are discussed here.
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