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PMID:10684855

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Citation

Zhong, S, Salomoni, P, Ronchetti, S, Guo, A, Ruggero, D and Pandolfi, PP (2000) Promyelocytic leukemia protein (PML) and Daxx participate in a novel nuclear pathway for apoptosis. J. Exp. Med. 191:631-40

Abstract

The promyelocytic leukemia protein (PML) gene of acute promyelocytic leukemia (APL) encodes a cell growth and tumor suppressor essential for multiple apoptotic signals. Daxx was identified as a molecule important for the cytoplasmic transduction of the Fas proapoptotic stimulus. Here, we show that upon mitogenic activation of mature splenic lymphocytes, Daxx is dramatically upregulated and accumulates in the PML nuclear body (NB) where PML and Daxx physically interact. In the absence of PML, Daxx acquires a dispersed nuclear pattern, and activation-induced cell death of splenocytes is profoundly impaired. PML inactivation results in the complete abrogation of the Daxx proapoptotic ability. In APL cells, Daxx is delocalized from the NB. Upon retinoic acid treatment, which induces disease remission in APL, Daxx relocalizes to the PML NBs. These results indicate that PML and Daxx cooperate in a novel NB-dependent pathway for apoptosis and shed new light in the role of PML in tumor suppression.

Links

PubMed PMC2195846

Keywords

Animals; Apoptosis/physiology; COS Cells; Carrier Proteins/metabolism; Cell Nucleus/physiology; Cell Nucleus/ultrastructure; Intracellular Signaling Peptides and Proteins; Lymphocyte Activation; Lymphocytes/cytology; Lymphocytes/physiology; Male; Mice; Mice, Knockout; Neoplasm Proteins/deficiency; Neoplasm Proteins/genetics; Neoplasm Proteins/metabolism; Nuclear Proteins/metabolism; Recombinant Proteins/metabolism; Signal Transduction; Spleen/immunology; Testis/metabolism; Transcription Factors/deficiency; Transcription Factors/genetics; Transcription Factors/metabolism; Transfection; Tumor Suppressor Proteins

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:DAXX

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P29590

F

Seeded From UniProt

complete

MOUSE:DAXX

located_in

GO:0005829: cytosol

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:DAXX

located_in

GO:0016605: PML body

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:DAXX

acts_upstream_of_or_within

GO:2001235: positive regulation of apoptotic signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:DAXX

acts_upstream_of_or_within

GO:2001235: positive regulation of apoptotic signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:104662

P

Seeded From UniProt

complete

HUMAN:PML

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O35613

F

Seeded From UniProt

complete

MOUSE:PML

acts_upstream_of_or_within

GO:2001235: positive regulation of apoptotic signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1197015

P

Seeded From UniProt

complete

MOUSE:PML

acts_upstream_of_or_within

GO:2001235: positive regulation of apoptotic signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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