P300-mediated Acetylation of Human Transcriptional Coactivator PC4 Is Inhibited by Phosphorylation

B R Prashanth Kumar,V Swaminathan,Sourav Banerjee,Tapas K Kundu

doi:10.1074/jbc.m100934200

B R Prashanth Kumar, V Swaminathan + Show 2 more

Open Access

https://doi.org/10.1074/jbc.m100934200

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Abstract

The human positive coactivator 4 (PC4) acts as a general coactivator for activator-dependent transcription, the activity of which is regulated negatively by phosphorylation. We report here that PC4 can be acetylated specifically by another coactivator, p300. Interestingly, phosphorylation of PC4 by casein kinase II inhibits the p300-mediated acetylation. Mass spectral analysis revealed that there are at least two lysine residues acetylated in PC4, as a result of which its DNA binding activity is stimulated.

Highlights

Human positive coactivator 4 (PC4)1 was isolated from a mammalian cofactor activity, upstream stimulatory activity, independently by two different groups
Mass spectral analysis revealed that there are at least two lysine residues acetylated in PC4, as a result of which its DNA binding activity is stimulated
Mutation and mass spectrometric analyses suggest that phosphorylation of PC4 in vivo is mediated by casein kinase II (CKII), and it is restricted to seven serine residues between 2 and 28 at the N

Summary

Introduction

Human positive coactivator 4 (PC4)1 was isolated from a mammalian cofactor activity, upstream stimulatory activity, independently by two different groups. Mass spectral analysis revealed that there are at least two lysine residues acetylated in PC4, as a result of which its DNA binding activity is stimulated. PC4 is subjected to in vivo phosphorylation events that negatively regulate its coactivator function and its interactions with the activator and TATA box-binding protein/TFIIA [2, 7].

Results

Conclusion