The transcriptional integrator CREB-binding protein mediates positive cross talk between nuclear hormone receptors and the hematopoietic bZip protein p45/NF-E2.
Thyroid hormone (T3) and retinoic acid (RA) play important roles in erythropoiesis. We found that the hematopoietic cell-specific bZip protein p45/NF-E2 interacts with T3 receptor (TR) and RA receptor (RAR) but not retinoid X receptor. The interaction is between the DNA-binding domain of the nuclear receptor and the leucine zipper region of p45/NF-E2 but is markedly enhanced by cognate ligand. Remarkably, ligand-dependent transactivation by TR and RAR is markedly potentiated by p45/NF-E2. This effect of p45/NF-E2 is prevented by maf-like protein p18, which functions positively as a heterodimer with p45/NF-E2 on DNA. Potentiation of hormone action by p45/NF-E2 requires its activation domain, which interacts strongly with the multifaceted coactivator cyclic AMP response element protein-binding protein (CBP). The region of CBP which interacts with p45/NF-E2 is the same interaction domain that mediates inhibition of hormone-stimulated transcription by AP1 transcription factors. Overexpression of the bZip interaction domain of CBP specifically abolishes the positive cross talk between TR and p45/NF-E2. Thus, positive cross talk between p45/NF-E2 and nuclear hormone receptors requires direct protein-protein interactions between these factors and with CBP, whose integration of positive signals from two transactivation domains provides a novel mechanism for potentiation of hormone action in hematopoietic cells.
Cheng
X
X
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-6149, USA.
Reginato
M J
MJ
Andrews
N C
NC
Lazar
M A
MA
D000818:Animals; D019556:COS Cells; D050882:CREB-Binding Protein; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D050981:Erythroid-Specific DNA-Binding Factors; D016350:Leucine Zippers; D050985:MafK Transcription Factor; D008958:Models, Molecular; D050984:NF-E2 Transcription Factor, p45 Subunit; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D051256:Oncogene Protein v-maf; D009856:Oncogene Proteins, Viral; D051381:Rats; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology*; D014284:Triiodothyronine / Q000494:pharmacology; D014764:Viral Proteins; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050985:MafK Transcription Factor; C494697:Mafk protein, rat; D050984:NF-E2 Transcription Factor, p45 Subunit; D009687:Nuclear Proteins; D051256:Oncogene Protein v-maf; D009856:Oncogene Proteins, Viral; C000607073:Rara protein, rat; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D011993:Recombinant Fusion Proteins; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; D015534:Trans-Activators; D014157:Transcription Factors; D014764:Viral Proteins; D014284:Triiodothyronine; D050882:CREB-Binding Protein; C494365:Crebbp protein, rat