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Assays for Validating Histone Acetyltransferase Inhibitors
09:11

Assays for Validating Histone Acetyltransferase Inhibitors

Published on: August 6, 2020

Inhibition of histone acetyltransferase function of p300 by PKCdelta

L W Yuan1, Jae-Won Soh, I Bernard Weinstein

  • 1Department of Physiology and Biophysics, School of Medicine, Boston University, 715 Albany St., MA 02118, USA. yuan1w01@yahoo.com

Biochimica Et Biophysica Acta
|October 16, 2002
PubMed

Insights

Protein kinase Cdelta (PKCdelta) phosphorylates p300, a key coactivator, inhibiting its HAT activity. This novel pathway suggests PKCdelta

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Signaling

Background:

  • Protein kinase Cdelta (PKCdelta) is a distinct isoform within the PKC family.
  • p300 functions as a histone acetyltransferase (HAT) and transcription coactivator.
  • Both PKCdelta and p300 are implicated in growth suppression, differentiation, and apoptosis.

Purpose of the Study:

  • To investigate the interaction and functional relationship between PKCdelta and p300.
  • To identify specific phosphorylation sites on p300 by PKCdelta.
  • To elucidate the impact of this phosphorylation on p300's HAT activity and coactivator function.

Main Methods:

  • In vitro kinase assays to determine PKCdelta's specificity.
  • In vivo studies to confirm phosphorylation in cellular contexts.
  • Assays to measure histone acetyltransferase (HAT) activity.
  • Analysis of nucleosomal histone acetylation levels.

Main Results:

  • PKCdelta specifically phosphorylates p300 at serine 89, both in vitro and in vivo.
  • This phosphorylation event inhibits the intrinsic HAT activity of p300.
  • Reduced p300 HAT activity leads to decreased acetylation of nucleosomal histones.
  • The transcription coactivator function of p300 is repressed.

Conclusions:

  • PKCdelta directly regulates p300 activity through phosphorylation at serine 89.
  • This novel signaling pathway mediated by PKCdelta inhibits p300's role in histone acetylation.
  • The findings suggest a mechanism by which PKCdelta may suppress cell growth and promote differentiation.

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