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Pathway Description
Acetylation and Deacetylation of RelA in The Nucleus
Homo sapiens
Protein Pathway
NF-kB transcription factor plays a role in the inflammatory and immune response of mammals. Acetylation of RelA regulates NF-kB activity. Tumor necrosis factor activates tumor necrosis factor receptor, recruiting proteins FADD, TRADD, RIP and TRAF6 to activate the NF-kB pathway. Activation of IKK complex causes the phosphorylation of I-kappa-B-alpha and triggers its degradation. I-kappa-B-alpha normally sequesters KF-kB in the cytoplasm, following its degradation, RELA and p50 (subunits of NF-kB) are liberated can translocate to the nucleus to activate gene expression. RelA and p50 associate with p300 and CREB transcriptional co-activators causing the acetylation of RelA and increase in transcriptional activity. Acetylated RelaA is targeted for deacetylation by transcriptional co-repressor Histone deacetylation 3 (HDAC3). This promotes its binding to I-kappa-B-alpha causing NF-kB's transport out of the nucleus and reduces its activity.
References
Acetylation and Deacetylation of RelA in The Nucleus References
https://cgap.nci.nih.gov/Pathways/BioCarta/m_RELAPathway
Chen LF, Mu Y, Greene WC: Acetylation of RelA at discrete sites regulates distinct nuclear functions of NF-kappaB. EMBO J. 2002 Dec 2;21(23):6539-48.
Pubmed: 12456660
Dai Y, Rahmani M, Dent P, Grant S: Blockade of histone deacetylase inhibitor-induced RelA/p65 acetylation and NF-kappaB activation potentiates apoptosis in leukemia cells through a process mediated by oxidative damage, XIAP downregulation, and c-Jun N-terminal kinase 1 activation. Mol Cell Biol. 2005 Jul;25(13):5429-44. doi: 10.1128/MCB.25.13.5429-5444.2005.
Pubmed: 15964800
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