UMMS Affiliation

Department of Pharmacology and Molecular Toxicology; Department of Cell Biology

Publication Date

2-12-2000

Document Type

Article

Subjects

Adaptor Proteins, Signal Transducing; Carrier Proteins; *Gene Expression Regulation, Neoplastic; Hela Cells; Humans; *Intracellular Signaling Peptides and Proteins; Leukemia, Promyelocytic, Acute; Neoplasm Proteins; Nuclear Proteins; Transcription Factors; *Transcription, Genetic; Tumor Suppressor Proteins

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

PML fuses with retinoic acid receptor alpha (RARalpha) in the t(15;17) translocation that causes acute promyelocytic leukemia (APL). In addition to localizing diffusely throughout the nucleoplasm, PML mainly resides in discrete nuclear structures known as PML oncogenic domains (PODs), which are disrupted in APL and spinocellular ataxia cells. We isolated the Fas-binding protein Daxx as a PML-interacting protein in a yeast two-hybrid screen. Biochemical and immunofluorescence analyses reveal that Daxx is a nuclear protein that interacts and colocalizes with PML in the PODs. Reporter gene assay shows that Daxx drastically represses basal transcription, likely by recruiting histone deacetylases. PML, but not its oncogenic fusion PML-RARalpha, inhibits the repressor function of Daxx. In addition, SUMO-1 modification of PML is required for sequestration of Daxx to the PODs and for efficient inhibition of Daxx-mediated transcriptional repression. Consistently, Daxx is found at condensed chromatin in cells that lack PML. These data suggest that Daxx is a novel nuclear protein bearing transcriptional repressor activity that may be regulated by interaction with PML.

Rights and Permissions

Citation: Mol Cell Biol. 2000 Mar;20(5):1784-96.

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Molecular and cellular biology

PubMed ID

10669754

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