Activating protein-1, nuclear factor-κB, and serum response factor as novel target molecules of the cancer-amplified transcription coactivator ASC-2

Soo-Kyung Lee, Soon Young Na, Sung Yun Jung, Ji Eun Choi, Byung Hak Jhun, JaeHun Cheong, Paul S. Meltzer, Young Chul Lee, Jae Lee

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

ASC-2 was recently discovered as a cancer-amplified transcription coactivator molecule of nuclear receptors, which interacts with multifunctional transcription integrators steroid receptor coactivator-1 (SRC-1) and CREB-binding protein (CBP)/p300. Herein, we report the identification of three mitogenic transcription factors as novel target molecules of ASC-2. First, the C-terminal transactivation domain of serum response factor (SRF) was identified among a series of ASC-2-interacting proteins from the yeast two-hybrid screening. Second, ASC-2 specifically interacted with the activating protein-1 (AP-1) components c-Jun and c-Fos as well as the nuclear factor-κB (NFκB) components p50 and p65, as demonstrated by the glutathione S-transferase pull-down assays as well as the yeast two-hybrid tests. In cotransfection of mammalian cells, ASC-2 potentiated transactivations by SRF, AP-1, and NFκB in a dose-dependent manner, either alone or in conjunction with SRC-1 and p300. In addition, ASC-2 efficiently relieved the previously described transrepression between nuclear receptors and either AP-1 or NFκB. Overall, these results suggest that the nuclear receptor coactivator ASC-2 also mediates transactivations by SRF, AP-1, and NFκB, which may contribute to the putative, ASC-2-mediated tumorigenesis.

Original languageEnglish (US)
Pages (from-to)915-925
Number of pages11
JournalMolecular Endocrinology
Volume14
Issue number6
DOIs
StatePublished - 2000
Externally publishedYes

Fingerprint

Serum Response Factor
Nuclear Receptor Coactivator 1
Nuclear Proteins
Transcriptional Activation
Nuclear Receptor Coactivator 2
Nuclear Receptor Coactivators
CREB-Binding Protein
Neoplasms
Fungal Proteins
Cytoplasmic and Nuclear Receptors
Glutathione Transferase
Carcinogenesis
Proteins
Transcription Factors
Yeasts

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

Activating protein-1, nuclear factor-κB, and serum response factor as novel target molecules of the cancer-amplified transcription coactivator ASC-2. / Lee, Soo-Kyung; Na, Soon Young; Jung, Sung Yun; Choi, Ji Eun; Jhun, Byung Hak; Cheong, JaeHun; Meltzer, Paul S.; Lee, Young Chul; Lee, Jae.

In: Molecular Endocrinology, Vol. 14, No. 6, 2000, p. 915-925.

Research output: Contribution to journalArticle

Lee, Soo-Kyung ; Na, Soon Young ; Jung, Sung Yun ; Choi, Ji Eun ; Jhun, Byung Hak ; Cheong, JaeHun ; Meltzer, Paul S. ; Lee, Young Chul ; Lee, Jae. / Activating protein-1, nuclear factor-κB, and serum response factor as novel target molecules of the cancer-amplified transcription coactivator ASC-2. In: Molecular Endocrinology. 2000 ; Vol. 14, No. 6. pp. 915-925.
@article{39d45bbf7e634368a43a82aaf332883a,
title = "Activating protein-1, nuclear factor-κB, and serum response factor as novel target molecules of the cancer-amplified transcription coactivator ASC-2",
abstract = "ASC-2 was recently discovered as a cancer-amplified transcription coactivator molecule of nuclear receptors, which interacts with multifunctional transcription integrators steroid receptor coactivator-1 (SRC-1) and CREB-binding protein (CBP)/p300. Herein, we report the identification of three mitogenic transcription factors as novel target molecules of ASC-2. First, the C-terminal transactivation domain of serum response factor (SRF) was identified among a series of ASC-2-interacting proteins from the yeast two-hybrid screening. Second, ASC-2 specifically interacted with the activating protein-1 (AP-1) components c-Jun and c-Fos as well as the nuclear factor-κB (NFκB) components p50 and p65, as demonstrated by the glutathione S-transferase pull-down assays as well as the yeast two-hybrid tests. In cotransfection of mammalian cells, ASC-2 potentiated transactivations by SRF, AP-1, and NFκB in a dose-dependent manner, either alone or in conjunction with SRC-1 and p300. In addition, ASC-2 efficiently relieved the previously described transrepression between nuclear receptors and either AP-1 or NFκB. Overall, these results suggest that the nuclear receptor coactivator ASC-2 also mediates transactivations by SRF, AP-1, and NFκB, which may contribute to the putative, ASC-2-mediated tumorigenesis.",
author = "Soo-Kyung Lee and Na, {Soon Young} and Jung, {Sung Yun} and Choi, {Ji Eun} and Jhun, {Byung Hak} and JaeHun Cheong and Meltzer, {Paul S.} and Lee, {Young Chul} and Jae Lee",
year = "2000",
doi = "10.1210/me.14.6.915",
language = "English (US)",
volume = "14",
pages = "915--925",
journal = "Molecular Endocrinology",
issn = "0888-8809",
publisher = "The Endocrine Society",
number = "6",

}

TY - JOUR

T1 - Activating protein-1, nuclear factor-κB, and serum response factor as novel target molecules of the cancer-amplified transcription coactivator ASC-2

AU - Lee, Soo-Kyung

AU - Na, Soon Young

AU - Jung, Sung Yun

AU - Choi, Ji Eun

AU - Jhun, Byung Hak

AU - Cheong, JaeHun

AU - Meltzer, Paul S.

AU - Lee, Young Chul

AU - Lee, Jae

PY - 2000

Y1 - 2000

N2 - ASC-2 was recently discovered as a cancer-amplified transcription coactivator molecule of nuclear receptors, which interacts with multifunctional transcription integrators steroid receptor coactivator-1 (SRC-1) and CREB-binding protein (CBP)/p300. Herein, we report the identification of three mitogenic transcription factors as novel target molecules of ASC-2. First, the C-terminal transactivation domain of serum response factor (SRF) was identified among a series of ASC-2-interacting proteins from the yeast two-hybrid screening. Second, ASC-2 specifically interacted with the activating protein-1 (AP-1) components c-Jun and c-Fos as well as the nuclear factor-κB (NFκB) components p50 and p65, as demonstrated by the glutathione S-transferase pull-down assays as well as the yeast two-hybrid tests. In cotransfection of mammalian cells, ASC-2 potentiated transactivations by SRF, AP-1, and NFκB in a dose-dependent manner, either alone or in conjunction with SRC-1 and p300. In addition, ASC-2 efficiently relieved the previously described transrepression between nuclear receptors and either AP-1 or NFκB. Overall, these results suggest that the nuclear receptor coactivator ASC-2 also mediates transactivations by SRF, AP-1, and NFκB, which may contribute to the putative, ASC-2-mediated tumorigenesis.

AB - ASC-2 was recently discovered as a cancer-amplified transcription coactivator molecule of nuclear receptors, which interacts with multifunctional transcription integrators steroid receptor coactivator-1 (SRC-1) and CREB-binding protein (CBP)/p300. Herein, we report the identification of three mitogenic transcription factors as novel target molecules of ASC-2. First, the C-terminal transactivation domain of serum response factor (SRF) was identified among a series of ASC-2-interacting proteins from the yeast two-hybrid screening. Second, ASC-2 specifically interacted with the activating protein-1 (AP-1) components c-Jun and c-Fos as well as the nuclear factor-κB (NFκB) components p50 and p65, as demonstrated by the glutathione S-transferase pull-down assays as well as the yeast two-hybrid tests. In cotransfection of mammalian cells, ASC-2 potentiated transactivations by SRF, AP-1, and NFκB in a dose-dependent manner, either alone or in conjunction with SRC-1 and p300. In addition, ASC-2 efficiently relieved the previously described transrepression between nuclear receptors and either AP-1 or NFκB. Overall, these results suggest that the nuclear receptor coactivator ASC-2 also mediates transactivations by SRF, AP-1, and NFκB, which may contribute to the putative, ASC-2-mediated tumorigenesis.

UR - http://www.scopus.com/inward/record.url?scp=0034465051&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034465051&partnerID=8YFLogxK

U2 - 10.1210/me.14.6.915

DO - 10.1210/me.14.6.915

M3 - Article

C2 - 10847592

AN - SCOPUS:0034465051

VL - 14

SP - 915

EP - 925

JO - Molecular Endocrinology

JF - Molecular Endocrinology

SN - 0888-8809

IS - 6

ER -