Aberrant association of promyelocytic leukemia protein-retinoic acid receptor-α with coactivators contributes to its ability to regulate gene expression

Erin L. Reineke, Heng Liu, Minh Lam, Yu Liu, Hung Ying Kao

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The aberrant association of promyelocytic leukemia protein-retinoic acid receptor-α (PML-RARα) with corepressor complexes is generally thought to contribute to the ability of PML-RARα to regulate transcription. We report here that PML-RARα acquires aberrant association with coactivators. We show that endogenous PML-RARα interacts with the histone acetyltransferases CBP, p300, and SRC-1 in a hormone-independent manner, an association not seen for RARα. This hormone-independent coactivator binding activity requires an intact ligand-binding domain and the NR box of the coactivators. Confocal microscopy studies demonstrate that exogenous PML-RARα sequesters and colocalizes with coactivators. These observations correlate with the ability of PML-RARα to attenuate the transcription activation of the Notch signaling downstream effector, CBF1, and of the glucocorticoid receptor. This includes attenuation of the glucocorticoid-induced leucine zipper (GILZ) and FLJ25390 target genes of the endogenous glucocorticoid receptor. Furthermore, treatment of NB4 cells with all-trans-retinoic acid, which promotes PML-RARα degradation, resulted in increased activation of GILZ. On the basis of these findings, we propose a model in which the hormone-independent association between PML-RARα and coactivators contributes to its ability to regulate gene expression.

Original languageEnglish
Pages (from-to)18584-18596
Number of pages13
JournalJournal of Biological Chemistry
Volume282
Issue number25
DOIs
Publication statusPublished - 2007 Jun 22

Fingerprint

Retinoic Acid Receptors
Gene expression
Association reactions
Gene Expression
Proteins
Leucine Zippers
Glucocorticoid Receptors
Hormones
Transcription
Glucocorticoids
Chemical activation
Histone Acetyltransferases
Co-Repressor Proteins
Promyelocytic Leukemia Protein
Confocal microscopy
Tretinoin
Confocal Microscopy
Transcriptional Activation
Genes
Ligands

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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title = "Aberrant association of promyelocytic leukemia protein-retinoic acid receptor-α with coactivators contributes to its ability to regulate gene expression",
abstract = "The aberrant association of promyelocytic leukemia protein-retinoic acid receptor-α (PML-RARα) with corepressor complexes is generally thought to contribute to the ability of PML-RARα to regulate transcription. We report here that PML-RARα acquires aberrant association with coactivators. We show that endogenous PML-RARα interacts with the histone acetyltransferases CBP, p300, and SRC-1 in a hormone-independent manner, an association not seen for RARα. This hormone-independent coactivator binding activity requires an intact ligand-binding domain and the NR box of the coactivators. Confocal microscopy studies demonstrate that exogenous PML-RARα sequesters and colocalizes with coactivators. These observations correlate with the ability of PML-RARα to attenuate the transcription activation of the Notch signaling downstream effector, CBF1, and of the glucocorticoid receptor. This includes attenuation of the glucocorticoid-induced leucine zipper (GILZ) and FLJ25390 target genes of the endogenous glucocorticoid receptor. Furthermore, treatment of NB4 cells with all-trans-retinoic acid, which promotes PML-RARα degradation, resulted in increased activation of GILZ. On the basis of these findings, we propose a model in which the hormone-independent association between PML-RARα and coactivators contributes to its ability to regulate gene expression.",
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Aberrant association of promyelocytic leukemia protein-retinoic acid receptor-α with coactivators contributes to its ability to regulate gene expression. / Reineke, Erin L.; Liu, Heng; Lam, Minh; Liu, Yu; Kao, Hung Ying.

In: Journal of Biological Chemistry, Vol. 282, No. 25, 22.06.2007, p. 18584-18596.

Research output: Contribution to journalArticle

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