A nuclear factor, ASC-2, as a cancer-amplified transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptors in vivo

Soo-Kyung Lee, Sarah L. Anzick, Ji Eun Choi, Lukas Bubendorf, Xin Yuan Guan, Yong Keun Jung, Olli P. Kallioniemi, Juha Kononen, Jeffrey M. Trent, David Azorsa, Byung Hak Jhun, Jae Hun Cheong, Young Chul Lee, Paul S. Meltzer, Jae Lee

Research output: Contribution to journalArticle

171 Citations (Scopus)

Abstract

Many transcription coactivators interact with nuclear receptors in a ligand- and C-terminal transactivation function (AF2)-dependent manner. We isolated a nuclear factor (designated ASC-2) with such properties by using the ligand-binding domain of retinoid X receptor as a bait in a yeast two- hybrid screening. ASC-2 also interacted with other nuclear receptors, including retinoic acid receptor, thyroid hormone receptor, estrogen receptor α, and glucocorticoid receptor, basal factors TFIIA and TBP, and transcription integrators CBP/p300 and SRC-1. In transient cotransfections, ASC-2, either alone or in conjunction with CBP/p300 and SRC-1, stimulated ligand-dependent transactivation by wild type nuclear receptors but not mutant receptors lacking the AF2 domain. Consistent with an idea that ASC-2 is essential for the nuclear receptor function in vivo, microinjection of anti-ASC-2 antibody abrogated the ligand-dependent transactivation of retinoic acid receptor, and this repression was fully relieved by coinjection of ASC-2-expression vector. Surprisingly, ASC-2 was identical to a gene previously identified during a search for genes amplified and overexpressed in breast and other human cancers. From these results, we concluded that ASC- 2 is a bona fide transcription coactivator molecule of nuclear receptors, and its altered expression may contribute to the development of cancers.

Original languageEnglish (US)
Pages (from-to)34283-34293
Number of pages11
JournalJournal of Biological Chemistry
Volume274
Issue number48
DOIs
StatePublished - Nov 26 1999
Externally publishedYes

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Cytoplasmic and Nuclear Receptors
Transcriptional Activation
Ligands
Transcription
Retinoic Acid Receptors
Neoplasms
Transcription Factor TFIIA
Nuclear Receptor Coactivators
TATA-Box Binding Protein
Retinoid X Receptors
Thyroid Hormone Receptors
Genes
Glucocorticoid Receptors
Microinjections
Estrogen Receptors
Breast
Yeasts
Yeast
Screening
Antibodies

ASJC Scopus subject areas

  • Biochemistry

Cite this

A nuclear factor, ASC-2, as a cancer-amplified transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptors in vivo. / Lee, Soo-Kyung; Anzick, Sarah L.; Choi, Ji Eun; Bubendorf, Lukas; Guan, Xin Yuan; Jung, Yong Keun; Kallioniemi, Olli P.; Kononen, Juha; Trent, Jeffrey M.; Azorsa, David; Jhun, Byung Hak; Cheong, Jae Hun; Lee, Young Chul; Meltzer, Paul S.; Lee, Jae.

In: Journal of Biological Chemistry, Vol. 274, No. 48, 26.11.1999, p. 34283-34293.

Research output: Contribution to journalArticle

Lee, S-K, Anzick, SL, Choi, JE, Bubendorf, L, Guan, XY, Jung, YK, Kallioniemi, OP, Kononen, J, Trent, JM, Azorsa, D, Jhun, BH, Cheong, JH, Lee, YC, Meltzer, PS & Lee, J 1999, 'A nuclear factor, ASC-2, as a cancer-amplified transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptors in vivo', Journal of Biological Chemistry, vol. 274, no. 48, pp. 34283-34293. https://doi.org/10.1074/jbc.274.48.34283
Lee, Soo-Kyung ; Anzick, Sarah L. ; Choi, Ji Eun ; Bubendorf, Lukas ; Guan, Xin Yuan ; Jung, Yong Keun ; Kallioniemi, Olli P. ; Kononen, Juha ; Trent, Jeffrey M. ; Azorsa, David ; Jhun, Byung Hak ; Cheong, Jae Hun ; Lee, Young Chul ; Meltzer, Paul S. ; Lee, Jae. / A nuclear factor, ASC-2, as a cancer-amplified transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptors in vivo. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 48. pp. 34283-34293.
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AU - Lee, Soo-Kyung

AU - Anzick, Sarah L.

AU - Choi, Ji Eun

AU - Bubendorf, Lukas

AU - Guan, Xin Yuan

AU - Jung, Yong Keun

AU - Kallioniemi, Olli P.

AU - Kononen, Juha

AU - Trent, Jeffrey M.

AU - Azorsa, David

AU - Jhun, Byung Hak

AU - Cheong, Jae Hun

AU - Lee, Young Chul

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