Non-proteolytic regulation of p53-mediated transcription through destabilization of the activator-promoter complex by the proteasomal ATPases

Young Chan Kim, Shwu Yuan Wu, Hyun-Suk Lim, Cheng Ming Chiang, Thomas Kodadek

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

It has been shown previously that sub-complexes of the 26 S proteasome can regulate gene expression via non-proteolytic mechanisms. One such mechanism is the disruption of activator-promoter complexes in an ATP-dependent fashion, which was discovered in the context of the yeast Gal4 system. This activity strongly inhibits Gal4-driven gene expression unless the activator is mono-ubiquitylated, which protects it from the ATPases. To address whether this paradigm is also applicable to medically important mammalian transcriptional activators we report here a study of the interaction of the proteasomal ATPases with p53. It is shown that p53 binds directly to the ATPases via its C-terminal tetramerization and regulatory domain and that p53·promoter complexes are indeed vulnerable to ATPase-dependent disruption by the ATPase complex in vitro. Knockdown of one of the ATPases, Rpt6, in living cells results in increased occupancy of the p21waf1 promoter by p53 and increased expression of the gene, consistent with the idea that the proteasomal ATPases negatively regulate p53 function in a non-proteolytic fashion.

Original languageEnglish (US)
Pages (from-to)34522-34530
Number of pages9
JournalJournal of Biological Chemistry
Volume284
Issue number50
DOIs
StatePublished - Dec 11 2009
Externally publishedYes

Fingerprint

Transcription
Adenosine Triphosphatases
Gene Expression
Gene expression
Yeast
Genes
Adenosine Triphosphate
Yeasts
Cells

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Non-proteolytic regulation of p53-mediated transcription through destabilization of the activator-promoter complex by the proteasomal ATPases. / Kim, Young Chan; Wu, Shwu Yuan; Lim, Hyun-Suk; Chiang, Cheng Ming; Kodadek, Thomas.

In: Journal of Biological Chemistry, Vol. 284, No. 50, 11.12.2009, p. 34522-34530.

Research output: Contribution to journalArticle

@article{ac41b0e4709f4b57af37258181152759,
title = "Non-proteolytic regulation of p53-mediated transcription through destabilization of the activator-promoter complex by the proteasomal ATPases",
abstract = "It has been shown previously that sub-complexes of the 26 S proteasome can regulate gene expression via non-proteolytic mechanisms. One such mechanism is the disruption of activator-promoter complexes in an ATP-dependent fashion, which was discovered in the context of the yeast Gal4 system. This activity strongly inhibits Gal4-driven gene expression unless the activator is mono-ubiquitylated, which protects it from the ATPases. To address whether this paradigm is also applicable to medically important mammalian transcriptional activators we report here a study of the interaction of the proteasomal ATPases with p53. It is shown that p53 binds directly to the ATPases via its C-terminal tetramerization and regulatory domain and that p53·promoter complexes are indeed vulnerable to ATPase-dependent disruption by the ATPase complex in vitro. Knockdown of one of the ATPases, Rpt6, in living cells results in increased occupancy of the p21waf1 promoter by p53 and increased expression of the gene, consistent with the idea that the proteasomal ATPases negatively regulate p53 function in a non-proteolytic fashion.",
author = "Kim, {Young Chan} and Wu, {Shwu Yuan} and Hyun-Suk Lim and Chiang, {Cheng Ming} and Thomas Kodadek",
year = "2009",
month = "12",
day = "11",
doi = "10.1074/jbc.M109.017277",
language = "English (US)",
volume = "284",
pages = "34522--34530",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "50",

}

TY - JOUR

T1 - Non-proteolytic regulation of p53-mediated transcription through destabilization of the activator-promoter complex by the proteasomal ATPases

AU - Kim, Young Chan

AU - Wu, Shwu Yuan

AU - Lim, Hyun-Suk

AU - Chiang, Cheng Ming

AU - Kodadek, Thomas

PY - 2009/12/11

Y1 - 2009/12/11

N2 - It has been shown previously that sub-complexes of the 26 S proteasome can regulate gene expression via non-proteolytic mechanisms. One such mechanism is the disruption of activator-promoter complexes in an ATP-dependent fashion, which was discovered in the context of the yeast Gal4 system. This activity strongly inhibits Gal4-driven gene expression unless the activator is mono-ubiquitylated, which protects it from the ATPases. To address whether this paradigm is also applicable to medically important mammalian transcriptional activators we report here a study of the interaction of the proteasomal ATPases with p53. It is shown that p53 binds directly to the ATPases via its C-terminal tetramerization and regulatory domain and that p53·promoter complexes are indeed vulnerable to ATPase-dependent disruption by the ATPase complex in vitro. Knockdown of one of the ATPases, Rpt6, in living cells results in increased occupancy of the p21waf1 promoter by p53 and increased expression of the gene, consistent with the idea that the proteasomal ATPases negatively regulate p53 function in a non-proteolytic fashion.

AB - It has been shown previously that sub-complexes of the 26 S proteasome can regulate gene expression via non-proteolytic mechanisms. One such mechanism is the disruption of activator-promoter complexes in an ATP-dependent fashion, which was discovered in the context of the yeast Gal4 system. This activity strongly inhibits Gal4-driven gene expression unless the activator is mono-ubiquitylated, which protects it from the ATPases. To address whether this paradigm is also applicable to medically important mammalian transcriptional activators we report here a study of the interaction of the proteasomal ATPases with p53. It is shown that p53 binds directly to the ATPases via its C-terminal tetramerization and regulatory domain and that p53·promoter complexes are indeed vulnerable to ATPase-dependent disruption by the ATPase complex in vitro. Knockdown of one of the ATPases, Rpt6, in living cells results in increased occupancy of the p21waf1 promoter by p53 and increased expression of the gene, consistent with the idea that the proteasomal ATPases negatively regulate p53 function in a non-proteolytic fashion.

UR - http://www.scopus.com/inward/record.url?scp=71749097048&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=71749097048&partnerID=8YFLogxK

U2 - 10.1074/jbc.M109.017277

DO - 10.1074/jbc.M109.017277

M3 - Article

VL - 284

SP - 34522

EP - 34530

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 50

ER -