Multimeric complexes of the PML-retinoic acid receptor alpha fusion protein in acute promyelocytic leukemia cells and interference with retinoid and peroxisome-proliferator signaling pathways.

Details

Serval ID
serval:BIB_06DDCEAF003C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Multimeric complexes of the PML-retinoic acid receptor alpha fusion protein in acute promyelocytic leukemia cells and interference with retinoid and peroxisome-proliferator signaling pathways.
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(s)
Jansen J.H., Mahfoudi A., Rambaud S., Lavau C., Wahli W., Dejean A.
ISSN
0027-8424[print], 0027-8424[linking]
Publication state
Published
Issued date
08/1995
Volume
92
Number
16
Pages
7401-7405
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
The t(15;17) chromosomal translocation, specific for acute promyelocytic leukemia (APL), fuses the PML gene to the retinoic acid receptor alpha (RAR alpha) gene, resulting in expression of a PML-RAR alpha hybrid protein. In this report, we analyzed the nature of PML-RAR alpha-containing complexes in nuclear protein extracts of t(15;17)-positive cells. We show that endogenous PML-RAR alpha can bind to DNA as a homodimer, in contrast to RAR alpha that requires the retinoid X receptor (RXR) dimerization partner. In addition, these cells contain oligomeric complexes of PML-RAR alpha and endogenous RXR. Treatment with retinoic acid results in a decrease of PML-RAR alpha protein levels and, as a consequence, of DNA binding by the different complexes. Using responsive elements from various hormone signaling pathways, we show that PML-RAR alpha homodimers have altered DNA-binding characteristics when compared to RAR alpha-RXR alpha heterodimers. In transfected Drosophila SL-3 cells that are devoid of endogenous retinoid receptors PML-RAR alpha inhibits transactivation by RAR alpha-RXR alpha heterodimers in a dominant fashion. In addition, we show that both normal retinoid receptors and the PML-RAR alpha hybrid bind and activate the peroxisome proliferator-activated receptor responsive element from the Acyl-CoA oxidase gene, indicating that retinoids and peroxisome proliferator receptors may share common target genes. These properties of PML-RAR alpha may contribute to the transformed phenotype of APL cells.
Keywords
Animals, Binding Sites, Chromosomes, Human, Pair 15, Chromosomes, Human, Pair 17, DNA/metabolism, Drosophila, Hela Cells, Humans, Leukemia, Promyelocytic, Acute/genetics, Leukemia, Promyelocytic, Acute/metabolism, Mice, Neoplasm Proteins/chemistry, Neoplasm Proteins/genetics, Oncogene Proteins, Fusion/chemistry, Oncogene Proteins, Fusion/genetics, Protein Conformation, Receptors, Cytoplasmic and Nuclear/metabolism, Receptors, Retinoic Acid/metabolism, Retinoid X Receptors, Signal Transduction, Transcription Factors/metabolism, Transcriptional Activation, Translocation, Genetic
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 16:04
Last modification date
20/08/2019 12:29
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