Duration of Nuclear NF-κB Action Regulated by Reversible Acetylation

  title={Duration of Nuclear NF-$\kappa$B Action Regulated by Reversible Acetylation},
  author={Lin-Feng Chen and Wolfgang Fischle and Eric Verdin and Warner C. Greene},
  pages={1653 - 1657}
The nuclear expression and action of the nuclear factor kappa B (NF-κB) transcription factor requires signal-coupled phosphorylation and degradation of the IκB inhibitors, which normally bind and sequester this pleiotropically active factor in the cytoplasm. The subsequent molecular events that regulate the termination of nuclear NF-κB action remain poorly defined, although the activation of de novo IκBα gene expression by NF-κB likely plays a key role. Our studies now demonstrate that the RelA… 
Regulation of distinct biological activities of the NF-κB transcription factor complex by acetylation
Although the proximal cytoplasmic signaling events that control the activation of the NF-κB transcription factor are understood in considerable detail, the subsequent intranuclear events that
Post-activation Turn-off of NF-κB-dependent Transcription Is Regulated by Acetylation of p65*
This work shows that the p65 subunit of NF-κB is acetylated by both p300 and PCAF on lysines 122 and 123 and proposes that acetylation of p65 plays a key role in IκΒα-mediated attenuation ofNF-κΓ transcriptional activity which is an important process that restores the latent state in post-induced cells.
Assessing acetylation of NF-κB
Regulation of NF-κB activity by competition between RelA acetylation and ubiquitination
Reconstitution of rela−/− fibroblasts with wild-type and mutant forms of RelA revealed that modifications at these residues can have activating and inhibitory functions depending on the target gene context.
Brd4 Coactivates Transcriptional Activation of NF-κB via Specific Binding to Acetylated RelA
Brd4 is identified as a novel coactivator of NF-κB through specifically binding to acetylated lysine-310 of RelA, and a mechanism by which acetylation of the RelA subunit stimulates the transcriptional activity of NF -κB and the NF-σκB-dependent inflammatory response is revealed.
Transcription Factor NF-κ B: Function, Structure, Regulation, Pathways, and Applications
The role of NF-κB in learning is discussed, a hint that NF-σB has functions beyond those traditionally associated with it, and modern drugs used to inhibit it are reviewed.


Transcriptional Activation by NF-κB Requires Multiple Coactivators
It is demonstrated that NF-κB recruits a coactivator complex that has striking similarities to that recruited by nuclear receptors, and this findings provide new mechanistic insights into how this family of dimeric transcription factors has a differential effect on gene expression.
Regulation of NF-κB by Cyclin-Dependent Kinases Associated with the p300 Coactivator
The interaction of NF-κB and CDKs through the p300 and CBP coactivators provides a mechanism for the coordination of transcriptional activation with cell cycle progression.
How NF-κB is activated: the role of the IκB kinase (IKK) complex
This review describes the identification of proteins in the IKK complex, and the regulation and physiological functions of IKK.
THE NF-κB AND IκB PROTEINS: New Discoveries and Insights
▪ Abstract The transcription factor NF-κB has attracted widespread attention among researchers in many fields based on the following: its unusual and rapid regulation, the wide range of genes that it
Mutual regulation of the transcriptional activator NF-kappa B and its inhibitor, I kappa B-alpha.
It is demonstrated here with human T lymphocytes and monocytes that different stimuli, including tumor necrosis factor alpha and phorbol 12-myristate 13-acetate, cause rapid degradation of I kappa B-alpha, with concomitant activation of NF-kappa B, followed by a dramatic increase in I k Kappa B- alpha mRNA and protein synthesis.
Acetylation by PCAF Enhances CIITA Nuclear Accumulation and Transactivation of Major Histocompatibility Complex Class II Genes
It is demonstrated that in addition to CBP, PCAF binds toCIITA both in vivo and in vitro and enhances CIITA-dependent transcriptional activation of class II promoters and supports a novel function for acetylation, i.e., to regulate gene expression by stimulating the nuclear accumulation of an activator.
Nuclear localization of I kappa B alpha promotes active transport of NF-kappa B from the nucleus to the cytoplasm.
In the present work, it is reported that I kappa B alpha, when expressed in the nuclear compartment, not only abrogates NF-kappa B/DNA interactions and NF-cappa B-dependent transcription, but also transports NF-Kappa B back to the cytoplasm.
Inducible nuclear expression of newly synthesized I kappa B alpha negatively regulates DNA-binding and transcriptional activities of NF-kappa B.
Following the appearance of I kappa B alpha in the nuclei of activated cells, a dramatic reduction in the amount of nuclear p50 occurs, suggesting that NF-kappa B-I kappaB alpha complexes are cleared from the nucleus.
NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses.
Recently, significant advances have been made in elucidating the details of the pathways through which signals are transmitted to the NF-kappa B:I kappa B complex in the cytosol and their implications for the study of NF-Kappa B.