The DRIP complex and SRC-1/p160 coactivators share similar nuclear receptor binding determinants but constitute functionally distinct complexes

Christophe Rachez, Matthew J. Gamble, Chao Pei Betty Chang, G. Brandon Atkins, Mitchell A. Lazar, Leonard P. Freedman

Research output: Contribution to journalArticle

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Abstract

Transcriptional activation requires both access to DNA assembled as chromatin and functional contact with components of the basal transcription machinery. Using the hormone-bound vitamin D3 receptor (VDR) ligand binding domain (LBD) as an affinity matrix, we previously identified a novel multisubunit coactivator complex, DRIP (VDR-interacting proteins), required for transcriptional activation by nuclear receptors and several other transcription factors. In this report, we characterize the nuclear receptor binding features of DRIP205, a key subunit of the DRIP complex, that interacts directly with VDR and thyroid hormone receptor in response to ligand and anchors the other DRIP subunits to the nuclear receptor LBD. In common with other nuclear receptor coactivators, DRIP205 interaction occurs through one of two LXXLL motifs and requires the receptor's AF-2 subdomain. Although the second motif of DRIP205 is required only for VDR binding in vitro, both motifs are used in the context of an retinoid X receptor-VDR heterodimer on DNA and in transactivation in vivo. We demonstrate that both endogenous p160 coactivators and DRIP complexes bind to the VDR LBD from nuclear extracts through similar sequence requirements, but they do so as distinct complexes. Moreover, in contrast to the p160 family of coactivators, the DRIP complex is devoid of any histone acetyltransferase activity. The results demonstrate that different coactivator complexes with distinct functions bind to the same transactivation region of nuclear receptors, suggesting that they are both required for transcription activation by nuclear receptors.

Original languageEnglish (US)
Pages (from-to)2718-2726
Number of pages9
JournalMolecular and Cellular Biology
Volume20
Issue number8
DOIs
StatePublished - Apr 2000
Externally publishedYes

Fingerprint

Calcitriol Receptors
Cytoplasmic and Nuclear Receptors
Mediator Complex Subunit 1
Transcriptional Activation
Ligands
Nuclear Receptor Coactivators
Furylfuramide
Receptor-Interacting Protein Serine-Threonine Kinases
Retinoid X Receptors
Histone Acetyltransferases
Thyroid Hormone Receptors
DNA
Chromatin
VDR interacting protein complex DRIP
Transcription Factors
Hormones

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

The DRIP complex and SRC-1/p160 coactivators share similar nuclear receptor binding determinants but constitute functionally distinct complexes. / Rachez, Christophe; Gamble, Matthew J.; Chang, Chao Pei Betty; Atkins, G. Brandon; Lazar, Mitchell A.; Freedman, Leonard P.

In: Molecular and Cellular Biology, Vol. 20, No. 8, 04.2000, p. 2718-2726.

Research output: Contribution to journalArticle

Rachez, Christophe ; Gamble, Matthew J. ; Chang, Chao Pei Betty ; Atkins, G. Brandon ; Lazar, Mitchell A. ; Freedman, Leonard P. / The DRIP complex and SRC-1/p160 coactivators share similar nuclear receptor binding determinants but constitute functionally distinct complexes. In: Molecular and Cellular Biology. 2000 ; Vol. 20, No. 8. pp. 2718-2726.
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