Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 191, Issue 4, Pages 631-639Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.191.4.631
Keywords
apoptosis; PML; Daxx; nuclear body; acute promyelocytic leukemia
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Funding
- NCI NIH HHS [R37 CA071692, CA71692, R01 CA071692, CA08748, P30 CA008748] Funding Source: Medline
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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 NE. 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.
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