Regulation of the p300 HAT domain via a novel activation loop

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Publication Date


Document Type



Acetyl Coenzyme A; Acetylation; Acetyltransferases; Amino Acid Sequence; Animals; Cloning, Molecular; Conserved Sequence; DNA Primers; Enzyme Activation; Escherichia coli; Escherichia coli Proteins; Gene Expression Regulation, Enzymologic; Histone Acetyltransferases; Kinetics; Molecular Sequence Data; Recombinant Proteins; Sequence Alignment; Sequence Homology, Amino Acid


Biochemistry | Enzymes and Coenzymes | Medicinal-Pharmaceutical Chemistry | Therapeutics


The transcriptional coactivator p300 is a histone acetyltransferase (HAT) whose function is critical for regulating gene expression in mammalian cells. However, the molecular events that regulate p300 HAT activity are poorly understood. We evaluated autoacetylation of the p300 HAT protein domain to determine its function. Using expressed protein ligation, the p300 HAT protein domain was generated in hypoacetylated form and found to have reduced catalytic activity. This basal catalytic rate was stimulated by autoacetylation of several key lysine sites within an apparent activation loop motif. This post-translational modification and catalytic regulation of p300 HAT activity is conceptually analogous to the activation of most protein kinases by autophosphorylation. We therefore propose that this autoregulatory loop could influence the impact of p300 on a wide variety of signaling and transcriptional events.

DOI of Published Version



Nat Struct Mol Biol. 2004 Apr;11(4):308-15. Epub 2004 Mar 7. Link to article on publisher's site

Journal/Book/Conference Title

Nature structural and molecular biology


At the time of publication, Paul Thompson was not yet affiliated with UMass Medical School.

Related Resources

Link to Article in PubMed