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Title: NUCLEOPHOSMIN/B23 NEGATIVELY REGULATES GCN5-DEPENDENT HISTONE ACETYLATION AND TRANSACTIVATION

Abstract

Nucleophosmin/B23 is a multifunctional phosphoprotein that is overexpressed in cancer cells and has been shown to be involved in both positive and negative regulation of transcription. In this study, we first identified GCN5 acetyltransferase as a B23-interacting protein by mass spectrometry, which was then confirmed by in vivo co-immunoprecipitation. In vitro assay demonstrated that B23 bound the PCAF-N domain of GCN5 and inhibited GCN5-mediated acetylation of both free and mononucleosomal histones, probably through interfering with GCN5 and masking histones from being acetylated. Mitotic B23 exhibited higher inhibitory activity on GCN5-mediated histone acetylation than interphase B23. Immunodepletion experiments of mitotic extracts revealed that phosphorylation of B23 at Thr199 enhanced the inhibition of GCN5-mediated histone acetylation. Moreover, luciferase reporter and microarray analyses suggested that B23 attenuated GCN5-mediated transactivation in vivo. Taken together, our studies suggest a molecular mechanism of B23 in the mitotic inhibition of GCN5-mediated histone acetylation and transactivation.

Authors:
 [1];  [1];  [1];  [2];  [3];  [1];  [1];  [3];  [1]
  1. ORNL
  2. Samuel Lunenfeld Res Inst., Canada
  3. National Institute on Aging, Baltimore
Publication Date:
Research Org.:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Mouse Genetics Research Facility
Sponsoring Org.:
Work for Others (WFO); USDOE Office of Science (SC)
OSTI Identifier:
931125
DOE Contract Number:
DE-AC05-00OR22725
Resource Type:
Journal Article
Resource Relation:
Journal Name: Journal of Biological Chemistry; Journal Volume: 283; Journal Issue: 9
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; ACETYLATION; HISTONES; IN VITRO; IN VIVO; LUCIFERASE; MASS SPECTROSCOPY; NEOPLASMS; PHOSPHOPROTEINS; PHOSPHORYLATION; PROTEINS; REGULATIONS; TRANSCRIPTION

Citation Formats

Zou, Yonglong, Wu, Jun, Giannone, Richard J, Boucher, Lorrie, Du, Hansen, Huang, Ying, Johnson, Dabney K, Liu, Yie, and Wang, Yisong. NUCLEOPHOSMIN/B23 NEGATIVELY REGULATES GCN5-DEPENDENT HISTONE ACETYLATION AND TRANSACTIVATION. United States: N. p., 2007. Web. doi:10.1074/jbc.M709932200.
Zou, Yonglong, Wu, Jun, Giannone, Richard J, Boucher, Lorrie, Du, Hansen, Huang, Ying, Johnson, Dabney K, Liu, Yie, & Wang, Yisong. NUCLEOPHOSMIN/B23 NEGATIVELY REGULATES GCN5-DEPENDENT HISTONE ACETYLATION AND TRANSACTIVATION. United States. doi:10.1074/jbc.M709932200.
Zou, Yonglong, Wu, Jun, Giannone, Richard J, Boucher, Lorrie, Du, Hansen, Huang, Ying, Johnson, Dabney K, Liu, Yie, and Wang, Yisong. Mon . "NUCLEOPHOSMIN/B23 NEGATIVELY REGULATES GCN5-DEPENDENT HISTONE ACETYLATION AND TRANSACTIVATION". United States. doi:10.1074/jbc.M709932200.
@article{osti_931125,
title = {NUCLEOPHOSMIN/B23 NEGATIVELY REGULATES GCN5-DEPENDENT HISTONE ACETYLATION AND TRANSACTIVATION},
author = {Zou, Yonglong and Wu, Jun and Giannone, Richard J and Boucher, Lorrie and Du, Hansen and Huang, Ying and Johnson, Dabney K and Liu, Yie and Wang, Yisong},
abstractNote = {Nucleophosmin/B23 is a multifunctional phosphoprotein that is overexpressed in cancer cells and has been shown to be involved in both positive and negative regulation of transcription. In this study, we first identified GCN5 acetyltransferase as a B23-interacting protein by mass spectrometry, which was then confirmed by in vivo co-immunoprecipitation. In vitro assay demonstrated that B23 bound the PCAF-N domain of GCN5 and inhibited GCN5-mediated acetylation of both free and mononucleosomal histones, probably through interfering with GCN5 and masking histones from being acetylated. Mitotic B23 exhibited higher inhibitory activity on GCN5-mediated histone acetylation than interphase B23. Immunodepletion experiments of mitotic extracts revealed that phosphorylation of B23 at Thr199 enhanced the inhibition of GCN5-mediated histone acetylation. Moreover, luciferase reporter and microarray analyses suggested that B23 attenuated GCN5-mediated transactivation in vivo. Taken together, our studies suggest a molecular mechanism of B23 in the mitotic inhibition of GCN5-mediated histone acetylation and transactivation.},
doi = {10.1074/jbc.M709932200},
journal = {Journal of Biological Chemistry},
number = 9,
volume = 283,
place = {United States},
year = {Mon Jan 01 00:00:00 EST 2007},
month = {Mon Jan 01 00:00:00 EST 2007}
}
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