| Health / Medical Topics |
RELA Pathway
The rel/NF-kB family of transcription factors regulates the activity of genes involved in the immune response, hematopoiesis, and inflammation. NF-kB is a complex of two proteins, p65 (rel) and p50. NF-kB is held inactive in the cytoplasm by I-kB, until signals initiated by TNF or several other factors lead to the phosphorylation and degradation of I-kB and the subsequent release of NF-kB to bind DNA and activate genes. The activation of transcription by NF-kB requires transcriptional coactivators such as p300 and CBP to interact with the rest of the transcriptional apparatus. These coactivators posses enzyme activity, acting to catalyze the posttranslational acetylation of proteins on lysine groups. Acetylation of histones has been known for some time to occur in transcriptionally active chromatin regions. Histone deacetylase (HDAC) enzymes reverse the acetylation of histones. As with other signals, there an off-switch as well as an on-switch for NF-kB activation. The signal to terminate gene activation by NF-kB involves regulation of NF-kB acetylation. P300 and CBP recruited by NF-kB to the transcriptional complex acetylate RelA. Acetylated NF-kB proteins do not interact with I-kB and so continue stimulating transcription. To turn off NF-kB dependent transcription, the histone deacetylase HDAC3 binds to and deacetylates RelA, which then interacts strongly with I-kB once again and is inactivated. The reformed complex of NF-kB and I-kB is exported from the nucleus to the cytoplasm where it replenishes the pool of inactive NF-kB awaiting the next activation signal. The activity of other proteins may also be regulated by acetylation in a similar manner. (NCI Thesaurus/BIOCARTA)
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