ANCCA, an estrogen-regulated AAA+ ATPase coactivator for ERα, is required for coregulator occupancy and chromatin modification

June X Zou, Alexey S. Revenko, Li B. Li, Abigael T. Gemo, Hongwu Chen

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

AAA+ proteins play crucial roles in diverse biological processes via their ATPase-driven remodeling of macromolecular complexes. Here we report our identification of an evolutionarily conserved AAA+ protein, ANCCA/pro2000, endowed with a bromodomain that is strongly induced by estrogen in human breast cancer cells and is a direct target of protooncogene ACTR/AIB1/SRC-3. We found that ANCCA associates directly with estrogen-bound estrogen receptor (ER) α and ACTR. It is selectively recruited, upon estrogen stimulation, to a subset of ERα target genes including cyclin D1, c-myc, and E2F1 and is required for their estrogen-induced expression as well as breast cancer cell proliferation. Further studies indicate that ANCCA binds and hydrolyzes ATP and is critical for recruitment of coregulator CBP and histone hyperacetylation at the ER target chromatin. Moreover, mutations at the ATP binding motifs rendered ANCCA defective as a coactivator in mediating estrogen induction of gene expression. Together, our findings reveal an unexpected layer of regulatory mechanism in hormone signaling mediated by ANCCA and suggest that hormone-induced assembly of transcriptional coregulator complexes at chromatin is a process facilitated by AAA+ ATPase proteins.

Original languageEnglish (US)
Pages (from-to)18067-18072
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number46
DOIs
StatePublished - Nov 13 2007

Fingerprint

Estrogen Receptors
Chromatin
Adenosine Triphosphatases
Estrogens
Adenosine Triphosphate
bcl-1 Genes
Hormones
Breast Neoplasms
Macromolecular Substances
Biological Phenomena
Proteins
Histones
Cell Proliferation
Gene Expression
Mutation

Keywords

  • AAA+ protein
  • Cell cycle
  • Nuclear receptors

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

ANCCA, an estrogen-regulated AAA+ ATPase coactivator for ERα, is required for coregulator occupancy and chromatin modification. / Zou, June X; Revenko, Alexey S.; Li, Li B.; Gemo, Abigael T.; Chen, Hongwu.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 46, 13.11.2007, p. 18067-18072.

Research output: Contribution to journalArticle

@article{a82797490ffb42f4bffb8666c9eae5de,
title = "ANCCA, an estrogen-regulated AAA+ ATPase coactivator for ERα, is required for coregulator occupancy and chromatin modification",
abstract = "AAA+ proteins play crucial roles in diverse biological processes via their ATPase-driven remodeling of macromolecular complexes. Here we report our identification of an evolutionarily conserved AAA+ protein, ANCCA/pro2000, endowed with a bromodomain that is strongly induced by estrogen in human breast cancer cells and is a direct target of protooncogene ACTR/AIB1/SRC-3. We found that ANCCA associates directly with estrogen-bound estrogen receptor (ER) α and ACTR. It is selectively recruited, upon estrogen stimulation, to a subset of ERα target genes including cyclin D1, c-myc, and E2F1 and is required for their estrogen-induced expression as well as breast cancer cell proliferation. Further studies indicate that ANCCA binds and hydrolyzes ATP and is critical for recruitment of coregulator CBP and histone hyperacetylation at the ER target chromatin. Moreover, mutations at the ATP binding motifs rendered ANCCA defective as a coactivator in mediating estrogen induction of gene expression. Together, our findings reveal an unexpected layer of regulatory mechanism in hormone signaling mediated by ANCCA and suggest that hormone-induced assembly of transcriptional coregulator complexes at chromatin is a process facilitated by AAA+ ATPase proteins.",
keywords = "AAA+ protein, Cell cycle, Nuclear receptors",
author = "Zou, {June X} and Revenko, {Alexey S.} and Li, {Li B.} and Gemo, {Abigael T.} and Hongwu Chen",
year = "2007",
month = "11",
day = "13",
doi = "10.1073/pnas.0705814104",
language = "English (US)",
volume = "104",
pages = "18067--18072",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "46",

}

TY - JOUR

T1 - ANCCA, an estrogen-regulated AAA+ ATPase coactivator for ERα, is required for coregulator occupancy and chromatin modification

AU - Zou, June X

AU - Revenko, Alexey S.

AU - Li, Li B.

AU - Gemo, Abigael T.

AU - Chen, Hongwu

PY - 2007/11/13

Y1 - 2007/11/13

N2 - AAA+ proteins play crucial roles in diverse biological processes via their ATPase-driven remodeling of macromolecular complexes. Here we report our identification of an evolutionarily conserved AAA+ protein, ANCCA/pro2000, endowed with a bromodomain that is strongly induced by estrogen in human breast cancer cells and is a direct target of protooncogene ACTR/AIB1/SRC-3. We found that ANCCA associates directly with estrogen-bound estrogen receptor (ER) α and ACTR. It is selectively recruited, upon estrogen stimulation, to a subset of ERα target genes including cyclin D1, c-myc, and E2F1 and is required for their estrogen-induced expression as well as breast cancer cell proliferation. Further studies indicate that ANCCA binds and hydrolyzes ATP and is critical for recruitment of coregulator CBP and histone hyperacetylation at the ER target chromatin. Moreover, mutations at the ATP binding motifs rendered ANCCA defective as a coactivator in mediating estrogen induction of gene expression. Together, our findings reveal an unexpected layer of regulatory mechanism in hormone signaling mediated by ANCCA and suggest that hormone-induced assembly of transcriptional coregulator complexes at chromatin is a process facilitated by AAA+ ATPase proteins.

AB - AAA+ proteins play crucial roles in diverse biological processes via their ATPase-driven remodeling of macromolecular complexes. Here we report our identification of an evolutionarily conserved AAA+ protein, ANCCA/pro2000, endowed with a bromodomain that is strongly induced by estrogen in human breast cancer cells and is a direct target of protooncogene ACTR/AIB1/SRC-3. We found that ANCCA associates directly with estrogen-bound estrogen receptor (ER) α and ACTR. It is selectively recruited, upon estrogen stimulation, to a subset of ERα target genes including cyclin D1, c-myc, and E2F1 and is required for their estrogen-induced expression as well as breast cancer cell proliferation. Further studies indicate that ANCCA binds and hydrolyzes ATP and is critical for recruitment of coregulator CBP and histone hyperacetylation at the ER target chromatin. Moreover, mutations at the ATP binding motifs rendered ANCCA defective as a coactivator in mediating estrogen induction of gene expression. Together, our findings reveal an unexpected layer of regulatory mechanism in hormone signaling mediated by ANCCA and suggest that hormone-induced assembly of transcriptional coregulator complexes at chromatin is a process facilitated by AAA+ ATPase proteins.

KW - AAA+ protein

KW - Cell cycle

KW - Nuclear receptors

UR - http://www.scopus.com/inward/record.url?scp=36749066161&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=36749066161&partnerID=8YFLogxK

U2 - 10.1073/pnas.0705814104

DO - 10.1073/pnas.0705814104

M3 - Article

VL - 104

SP - 18067

EP - 18072

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 46

ER -