Document Detail

PML induces a novel caspase-independent death process.
MedLine Citation:
PMID:  9806544     Owner:  NLM     Status:  MEDLINE    
PML nuclear bodies (NBs) are nuclear matrix-associated structures altered by viruses and oncogenes. We show here that PML overexpression induces rapid cell death, independent of de novo transcription and cell cycling. PML death involves cytoplasmic features of apoptosis in the absence of caspase-3 activation, and caspase inhibitors such as zVAD accelerate PML death. zVAD also accelerates interferon (IFN)-induced death, suggesting that PML contributes to IFN-induced apoptosis. The death effector BAX and the cdk inhibitor p27KIP1 are novel NB-associated proteins recruited by PML to these nuclear domains, whereas the acute promyelocytic leukaemia (APL) PML/RAR alpha oncoprotein delocalizes them. Arsenic enhances targeting of PML, BAX and p27KIP1 to NBs and synergizes with PML and IFN to induce cell death. Thus, cell death susceptibility correlates with NB recruitment of NB proteins. These findings reveal a novel cell death pathway that neither requires nor induces caspase-3 activation, and suggest that NBs participate in the control of cell survival.
F Quignon; F De Bels; M Koken; J Feunteun; J C Ameisen; H de Thé
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nature genetics     Volume:  20     ISSN:  1061-4036     ISO Abbreviation:  Nat. Genet.     Publication Date:  1998 Nov 
Date Detail:
Created Date:  1998-11-16     Completed Date:  1998-11-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9216904     Medline TA:  Nat Genet     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  259-65     Citation Subset:  IM    
CNRS UPR 9051, Laboratoire associé au comité de Paris de la ligue contre le cancer, Institut d'Hématologie de l'Université Paris VII, Hôpital St Louis, France.
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MeSH Terms
Apoptosis / drug effects,  genetics,  physiology*
Arsenic / pharmacology
Caspase 3
Caspases / physiology
Cell Cycle Proteins*
Cell Nucleus / physiology
Cells, Cultured
Cyclin-Dependent Kinase Inhibitor p27
Cysteine Proteinase Inhibitors / pharmacology
Enzyme Activation
Gene Expression
Interferon Type I, Recombinant / pharmacology
Microtubule-Associated Proteins / metabolism
Neoplasm Proteins / genetics,  physiology*
Nuclear Proteins*
Proto-Oncogene Proteins / metabolism
Proto-Oncogene Proteins c-bcl-2*
Transcription Factors / genetics,  physiology*
Tumor Suppressor Proteins*
bcl-2-Associated X Protein
Reg. No./Substance:
0/BAX protein, human; 0/Bax protein, rat; 0/Cdkn1b protein, rat; 0/Cell Cycle Proteins; 0/Cysteine Proteinase Inhibitors; 0/Interferon Type I, Recombinant; 0/Microtubule-Associated Proteins; 0/Neoplasm Proteins; 0/Nuclear Proteins; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/Transcription Factors; 0/Tumor Suppressor Proteins; 0/bcl-2-Associated X Protein; 143220-95-5/PML protein, human; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; 7440-38-2/Arsenic; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Casp3 protein, rat; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases
Comment In:
Nat Genet. 1998 Nov;20(3):220-2   [PMID:  9806533 ]

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