Human ADA3 binds to estrogen receptor (ER) and functions as a coactivator for ER-mediated transactivation

Gaoyuan Meng, Yongtong Zhao, Alo Nag, Musheng Zeng, Goberdhan Dimri, Qingshen Gao, David E. Wazer, Rakesh Kumar, Hamid Band, Vimla Band

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

We have recently identified the hABA3 protein, the human homologue of yeast transcriptional coactivator yADA3, as a novel HPV16 E6 target. Using ectopic expression approaches, we further demonstrated that hABA3 directly binds to the 9-cis retinoic acid receptors α and β, and functions as a coactivaior for retinoid receptor-mediated transcriptional activation. Here, we examined the role of endogenous hABA3 as a coactivator for estrogen receptor (ER), an important member of the nuclear hormone receptor superfamily. We show that ADA3 directly interacts with ERα and ERβ. Using the chromatin immunoprecipitation assay, we also show that hADA3 is a component of the activator complexes bound to the native ER response element within the promoter of the estrogen-responsive gene pS2. Furthermore, using an ER response element-luciferase reporter, we show that overexpression of ADA3 enhances the ERα- and ERβ-mediated sequence-specific transactivation. Reverse transcription-PCR analysis showed an ADA3-mediated increase in estrogen-induced expression of the endogenous pS2 gene. More importantly, using RNA interference against hADA3, we demonstrate that inhibition of endogenous hADA3 inhibited ER-mediated transactivation and the estrogen-induced increase in the expression of pS2, cathepsin D, and progesterone receptor, three widely known ER-responsive genes. The HPV E6 protein, by targeting hADA3 for degradation, inhibited the ERα-mediated transactivation and the protein expression of ER target genes. Thus, our results demonstrate that ADA3 directly binds to human estrogen receptor and enhances the transcription of ER-responsive genes, suggesting a broader role of mammalian hADA3 as a coactivator of nuclear hormone receptors and the potential role of these pathways in HPV oncogenesis.

Original languageEnglish (US)
Pages (from-to)54230-54240
Number of pages11
JournalJournal of Biological Chemistry
Volume279
Issue number52
DOIs
StatePublished - Dec 24 2004
Externally publishedYes

Fingerprint

Estrogen Receptors
Transcriptional Activation
Genes
Estrogens
Response Elements
Cytoplasmic and Nuclear Receptors
Transcription
Retinoid X Receptors
Cathepsin D
Chromatin Immunoprecipitation
Proteins
Retinoids
Protein Transport
Progesterone Receptors
RNA Interference
Luciferases
Reverse Transcription
Yeast
Chromatin
Carcinogenesis

ASJC Scopus subject areas

  • Biochemistry

Cite this

Human ADA3 binds to estrogen receptor (ER) and functions as a coactivator for ER-mediated transactivation. / Meng, Gaoyuan; Zhao, Yongtong; Nag, Alo; Zeng, Musheng; Dimri, Goberdhan; Gao, Qingshen; Wazer, David E.; Kumar, Rakesh; Band, Hamid; Band, Vimla.

In: Journal of Biological Chemistry, Vol. 279, No. 52, 24.12.2004, p. 54230-54240.

Research output: Contribution to journalArticle

Meng, Gaoyuan ; Zhao, Yongtong ; Nag, Alo ; Zeng, Musheng ; Dimri, Goberdhan ; Gao, Qingshen ; Wazer, David E. ; Kumar, Rakesh ; Band, Hamid ; Band, Vimla. / Human ADA3 binds to estrogen receptor (ER) and functions as a coactivator for ER-mediated transactivation. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 52. pp. 54230-54240.
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T1 - Human ADA3 binds to estrogen receptor (ER) and functions as a coactivator for ER-mediated transactivation

AU - Meng, Gaoyuan

AU - Zhao, Yongtong

AU - Nag, Alo

AU - Zeng, Musheng

AU - Dimri, Goberdhan

AU - Gao, Qingshen

AU - Wazer, David E.

AU - Kumar, Rakesh

AU - Band, Hamid

AU - Band, Vimla

PY - 2004/12/24

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AB - We have recently identified the hABA3 protein, the human homologue of yeast transcriptional coactivator yADA3, as a novel HPV16 E6 target. Using ectopic expression approaches, we further demonstrated that hABA3 directly binds to the 9-cis retinoic acid receptors α and β, and functions as a coactivaior for retinoid receptor-mediated transcriptional activation. Here, we examined the role of endogenous hABA3 as a coactivator for estrogen receptor (ER), an important member of the nuclear hormone receptor superfamily. We show that ADA3 directly interacts with ERα and ERβ. Using the chromatin immunoprecipitation assay, we also show that hADA3 is a component of the activator complexes bound to the native ER response element within the promoter of the estrogen-responsive gene pS2. Furthermore, using an ER response element-luciferase reporter, we show that overexpression of ADA3 enhances the ERα- and ERβ-mediated sequence-specific transactivation. Reverse transcription-PCR analysis showed an ADA3-mediated increase in estrogen-induced expression of the endogenous pS2 gene. More importantly, using RNA interference against hADA3, we demonstrate that inhibition of endogenous hADA3 inhibited ER-mediated transactivation and the estrogen-induced increase in the expression of pS2, cathepsin D, and progesterone receptor, three widely known ER-responsive genes. The HPV E6 protein, by targeting hADA3 for degradation, inhibited the ERα-mediated transactivation and the protein expression of ER target genes. Thus, our results demonstrate that ADA3 directly binds to human estrogen receptor and enhances the transcription of ER-responsive genes, suggesting a broader role of mammalian hADA3 as a coactivator of nuclear hormone receptors and the potential role of these pathways in HPV oncogenesis.

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