PML is essential for multiple apoptotic pathways Journal Article
| Authors: | Wang, Z. G.; Ruggero, D.; Ronchetti, S.; Zhong, S.; Gaboli, M.; Rivi, R.; Pandolfi, P. P. |
| Article Title: | PML is essential for multiple apoptotic pathways |
| Abstract: | The PML gene of acute promyelocytic leukaemia (APL) encodes a cell growth and tumour suppressor, however, the mechanisms by which PML suppresses tumorigenesis are poorly understood. We show here that Pml is required for Fas- and caspase-dependent DNA-damage-induced apoptosis. We also found that Pml is essential for induction of programmed cell death by Fas, tumour necrosis factor α (TNF), ceramide and type I and II interferons (IFNs). As a result, Pml(-/-) mice and cells are protected from the lethal effects of ionizing radiation and anti-Fas antibody. Pml is required for caspase 1 and caspase 3 activation upon exposure to these stimuli. The PML-RARα fusion protein of APL renders haemopoietic progenitor cells resistant to Fas-, TNF- and IFN-induced apoptosis with a lack of caspase 3 activation, thus acting as a Pml dominant-negative product. These results demonstrate that Pml is a mediator of multiple apoptotic signals, and implicate inhibition of apoptosis in the pathogenesis of APL. |
| Keywords: | controlled study; unclassified drug; pathogenesis; nonhuman; alpha interferon; animal cell; mouse; animals; mice; mice, knockout; animal tissue; dna damage; apoptosis; cell growth; fas antigen; neoplasm proteins; caspase 3; enzyme activation; caspase; caspases; transcription factors; nuclear proteins; tumor suppressor gene; leukemia, promyelocytic, acute; tumor necrosis factor alpha; tumor necrosis factor-alpha; tumor suppressor proteins; acute myeloblastic leukemia; oncogene proteins, fusion; ionizing radiation; ceramide; ceramides; interleukin 1beta converting enzyme; antigens, cd95; gene isolation; intraperitoneal drug administration; concanavalin a; interferons; male; female; priority journal; article |
| Journal Title: | Nature Genetics |
| Volume: | 20 |
| Issue: | 3 |
| ISSN: | 1061-4036 |
| Publisher: | Nature Publishing Group |
| Date Published: | 1998-11-01 |
| Start Page: | 266 |
| End Page: | 272 |
| Language: | English |
| DOI: | 10.1038/3073 |
| PUBMED: | 9806545 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 12 December 2016 -- Source: Scopus |
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