Promyelocytic leukemia protein (PML) and Daxx participate in a novel nuclear pathway for apoptosis Journal Article
| Authors: | Zhong, S.; Salomoni, P.; Ronchetti, S.; Guo, A.; Ruggero, D.; Pandolfi, P. P. |
| Article Title: | Promyelocytic leukemia protein (PML) and Daxx participate in a novel nuclear pathway for apoptosis |
| 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. |
| Keywords: | signal transduction; human cell; animals; mice; mice, knockout; apoptosis; cell growth; spleen; fas antigen; neoplasm proteins; gene product; protein interaction; transfection; cos cells; transcription factors; nuclear proteins; cancer inhibition; lymphocyte activation; intracellular signaling peptides and proteins; carrier proteins; tumor suppressor proteins; recombinant proteins; promyelocytic leukemia; remission; cell nucleus; lymphocytes; retinoic acid; testis; acute promyelocytic leukemia; pml; daxx; cell nucleus inclusion body; nuclear body; human; male; priority journal; article |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 191 |
| Issue: | 4 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2000-02-21 |
| Start Page: | 631 |
| End Page: | 639 |
| Language: | English |
| DOI: | 10.1084/jem.191.4.631 |
| PUBMED: | 10684855 |
| PROVIDER: | scopus |
| PMCID: | PMC2195846 |
| DOI/URL: | |
| Notes: | Export Date: 18 November 2015 -- Source: Scopus |
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