Distinct steady-state nuclear receptor coregulator complexes exist in vivo

Neil J. Mckenna, Zafar Nawaz, Sophia Y. Tsai, Ming Jer Tsai, Bert W. O'Malley

Research output: Contribution to journalArticle

141 Citations (Scopus)

Abstract

Transcriptional regulation by members of the nuclear hormone receptor superfamily is a modular process requiring the mediation of distinct subclasses of coregulators. These subclasses include members of the steroid receptor coactivator-1 (SRC-1) coactivator family, p300/CBP and their associated proteins, such as p300/CBP-associated factor, human homologs of SWI/SNF proteins such as BRG-1, and the less well-characterized E3 ubiquitin- protein ligases E6 papillomavirus protein-associated protein and receptor- potentiating factor-1. Because functional studies indicate that these coregulators may form higher order complexes, we analyzed stead-state complexes of different coregulator subclasses in vivo. T47D and HeLa cell lysates were subjected to biochemical fractionation and screened by immunoblotting using coregulator-specific antibodies. We show that different subclasses of nuclear receptor coregulators exhibit distinct fractionation profiles. Furthermore, evidence is provided that SRC-1 family members may exist in vivo in heteromultimeric forms with each other. In addition, we demonstrate that liganded PR is present in stable complexes containing SRC-1 and transcription intermediary factor 2 (TIF2) in vivo. Our results suggest that the assembly of large, modular transcriptional complexes by recruitment of distinct subclasses of preformed coregulator subcomplexes may be involved in transcriptional regulation by activated nuclear receptors.

Original languageEnglish
Pages (from-to)11697-11702
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number20
DOIs
StatePublished - Sep 29 1998
Externally publishedYes

Fingerprint

Nuclear Receptor Coactivator 1
Cytoplasmic and Nuclear Receptors
Nuclear Receptor Coactivator 2
p300-CBP Transcription Factors
Proteins
Ubiquitin-Protein Ligases
HeLa Cells
Immunoblotting
Antibodies

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Distinct steady-state nuclear receptor coregulator complexes exist in vivo. / Mckenna, Neil J.; Nawaz, Zafar; Tsai, Sophia Y.; Tsai, Ming Jer; O'Malley, Bert W.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 95, No. 20, 29.09.1998, p. 11697-11702.

Research output: Contribution to journalArticle

Mckenna, Neil J. ; Nawaz, Zafar ; Tsai, Sophia Y. ; Tsai, Ming Jer ; O'Malley, Bert W. / Distinct steady-state nuclear receptor coregulator complexes exist in vivo. In: Proceedings of the National Academy of Sciences of the United States of America. 1998 ; Vol. 95, No. 20. pp. 11697-11702.
@article{e0409125a614402e8b36a0526121740d,
title = "Distinct steady-state nuclear receptor coregulator complexes exist in vivo",
abstract = "Transcriptional regulation by members of the nuclear hormone receptor superfamily is a modular process requiring the mediation of distinct subclasses of coregulators. These subclasses include members of the steroid receptor coactivator-1 (SRC-1) coactivator family, p300/CBP and their associated proteins, such as p300/CBP-associated factor, human homologs of SWI/SNF proteins such as BRG-1, and the less well-characterized E3 ubiquitin- protein ligases E6 papillomavirus protein-associated protein and receptor- potentiating factor-1. Because functional studies indicate that these coregulators may form higher order complexes, we analyzed stead-state complexes of different coregulator subclasses in vivo. T47D and HeLa cell lysates were subjected to biochemical fractionation and screened by immunoblotting using coregulator-specific antibodies. We show that different subclasses of nuclear receptor coregulators exhibit distinct fractionation profiles. Furthermore, evidence is provided that SRC-1 family members may exist in vivo in heteromultimeric forms with each other. In addition, we demonstrate that liganded PR is present in stable complexes containing SRC-1 and transcription intermediary factor 2 (TIF2) in vivo. Our results suggest that the assembly of large, modular transcriptional complexes by recruitment of distinct subclasses of preformed coregulator subcomplexes may be involved in transcriptional regulation by activated nuclear receptors.",
author = "Mckenna, {Neil J.} and Zafar Nawaz and Tsai, {Sophia Y.} and Tsai, {Ming Jer} and O'Malley, {Bert W.}",
year = "1998",
month = "9",
day = "29",
doi = "10.1073/pnas.95.20.11697",
language = "English",
volume = "95",
pages = "11697--11702",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "20",

}

TY - JOUR

T1 - Distinct steady-state nuclear receptor coregulator complexes exist in vivo

AU - Mckenna, Neil J.

AU - Nawaz, Zafar

AU - Tsai, Sophia Y.

AU - Tsai, Ming Jer

AU - O'Malley, Bert W.

PY - 1998/9/29

Y1 - 1998/9/29

N2 - Transcriptional regulation by members of the nuclear hormone receptor superfamily is a modular process requiring the mediation of distinct subclasses of coregulators. These subclasses include members of the steroid receptor coactivator-1 (SRC-1) coactivator family, p300/CBP and their associated proteins, such as p300/CBP-associated factor, human homologs of SWI/SNF proteins such as BRG-1, and the less well-characterized E3 ubiquitin- protein ligases E6 papillomavirus protein-associated protein and receptor- potentiating factor-1. Because functional studies indicate that these coregulators may form higher order complexes, we analyzed stead-state complexes of different coregulator subclasses in vivo. T47D and HeLa cell lysates were subjected to biochemical fractionation and screened by immunoblotting using coregulator-specific antibodies. We show that different subclasses of nuclear receptor coregulators exhibit distinct fractionation profiles. Furthermore, evidence is provided that SRC-1 family members may exist in vivo in heteromultimeric forms with each other. In addition, we demonstrate that liganded PR is present in stable complexes containing SRC-1 and transcription intermediary factor 2 (TIF2) in vivo. Our results suggest that the assembly of large, modular transcriptional complexes by recruitment of distinct subclasses of preformed coregulator subcomplexes may be involved in transcriptional regulation by activated nuclear receptors.

AB - Transcriptional regulation by members of the nuclear hormone receptor superfamily is a modular process requiring the mediation of distinct subclasses of coregulators. These subclasses include members of the steroid receptor coactivator-1 (SRC-1) coactivator family, p300/CBP and their associated proteins, such as p300/CBP-associated factor, human homologs of SWI/SNF proteins such as BRG-1, and the less well-characterized E3 ubiquitin- protein ligases E6 papillomavirus protein-associated protein and receptor- potentiating factor-1. Because functional studies indicate that these coregulators may form higher order complexes, we analyzed stead-state complexes of different coregulator subclasses in vivo. T47D and HeLa cell lysates were subjected to biochemical fractionation and screened by immunoblotting using coregulator-specific antibodies. We show that different subclasses of nuclear receptor coregulators exhibit distinct fractionation profiles. Furthermore, evidence is provided that SRC-1 family members may exist in vivo in heteromultimeric forms with each other. In addition, we demonstrate that liganded PR is present in stable complexes containing SRC-1 and transcription intermediary factor 2 (TIF2) in vivo. Our results suggest that the assembly of large, modular transcriptional complexes by recruitment of distinct subclasses of preformed coregulator subcomplexes may be involved in transcriptional regulation by activated nuclear receptors.

UR - http://www.scopus.com/inward/record.url?scp=0032578450&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032578450&partnerID=8YFLogxK

U2 - 10.1073/pnas.95.20.11697

DO - 10.1073/pnas.95.20.11697

M3 - Article

C2 - 9751728

AN - SCOPUS:0032578450

VL - 95

SP - 11697

EP - 11702

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 - 20

ER -