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Promyelocytic leukemia protein PML inhibits Nur77-mediated transcription through specific functional interactions.
- Source :
-
Oncogene [Oncogene] 2002 May 30; Vol. 21 (24), pp. 3925-33. - Publication Year :
- 2002
-
Abstract
- The promyelocytic leukemia protein PML is a tumor and growth suppressor and plays an important role in a multiple pathways of apoptosis and regulation of cell cycle progression. Our previous studies and others also documented a role of PML in transcriptional regulation through its association with transcription coactivator CBP and transcription corepressor HDAC. Here, we showed that PML is a potent transcriptional repressor of Nur77, an orphan receptor and a member of the steroid receptor superfamily of proteins. We found that PML represses Nur77-mediated transactivation through a physical and functional interaction between the two proteins. PML interacts with Nur-77 in vitro in a GST-pull down assay and in vivo by coimmunoprecipitation assay. PML/Nur77 colocalized in vivo in a double immunofluorescent staining and confocal microscopic analysis. Our study further showed that the coiled-coil domain of PML interacts with the DNA-binding domain of Nur77 (amino acids 267-332). Electrophoretic mobility shift assay demonstrated that PML interferes with Nur77 DNA binding in a dose-dependent manner. This study indicates that PML interacts with the DNA-binding domain of Nur77 and represses transcription by preventing it from binding to the target promoter. This study supports a role of PML/Nur77 interaction in regulating cell growth and apoptosis.
- Subjects :
- Apoptosis
Cell Division
Cell Line
Cell Nucleus metabolism
DNA, Complementary metabolism
Dose-Response Relationship, Drug
Gene Expression Regulation, Neoplastic
Glutathione Transferase metabolism
Humans
Luciferases metabolism
Microscopy, Fluorescence
Nuclear Receptor Subfamily 4, Group A, Member 1
Plasmids metabolism
Precipitin Tests
Promyelocytic Leukemia Protein
Protein Binding
Protein Structure, Tertiary
Receptors, Cytoplasmic and Nuclear
Receptors, Steroid
Recombinant Fusion Proteins metabolism
Transcriptional Activation
Tumor Cells, Cultured
Tumor Suppressor Proteins
DNA-Binding Proteins metabolism
Neoplasm Proteins metabolism
Nuclear Proteins
Transcription Factors metabolism
Transcription, Genetic
Subjects
Details
- Language :
- English
- ISSN :
- 0950-9232
- Volume :
- 21
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- Oncogene
- Publication Type :
- Academic Journal
- Accession number :
- 12032831
- Full Text :
- https://doi.org/10.1038/sj.onc.1205491