| PML regulates apoptosis at endoplasmic reticulum by modulating calcium release. | |
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MedLine Citation:
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PMID: 21030605 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The promyelocytic leukemia (PML) tumor suppressor is a pleiotropic modulator of apoptosis. However, the molecular basis for such a diverse proapoptotic role is currently unknown. We show that extranuclear Pml was specifically enriched at the endoplasmic reticulum (ER) and at the mitochondria-associated membranes, signaling domains involved in ER-to-mitochondria calcium ion (Ca(2+)) transport and in induction of apoptosis. We found Pml in complexes of large molecular size with the inositol 1,4,5-trisphosphate receptor (IP(3)R), protein kinase Akt, and protein phosphatase 2a (PP2a). Pml was essential for Akt- and PP2a-dependent modulation of IP(3)R phosphorylation and in turn for IP(3)R-mediated Ca(2+) release from ER. Our findings provide a mechanistic explanation for the pleiotropic role of Pml in apoptosis and identify a pharmacological target for the modulation of Ca(2+) signals. |
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Authors:
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Carlotta Giorgi; Keisuke Ito; Hui-Kuan Lin; Clara Santangelo; Mariusz R Wieckowski; Magdalena Lebiedzinska; Angela Bononi; Massimo Bonora; Jerzy Duszynski; Rosa Bernardi; Rosario Rizzuto; Carlo Tacchetti; Paolo Pinton; Pier Paolo Pandolfi |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-10-28 |
Journal Detail:
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Title: Science (New York, N.Y.) Volume: 330 ISSN: 1095-9203 ISO Abbreviation: Science Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-11-26 Completed Date: 2010-12-10 Revised Date: 2013-05-23 |
Medline Journal Info:
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Nlm Unique ID: 0404511 Medline TA: Science Country: United States |
Other Details:
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Languages: eng Pagination: 1247-51 Citation Subset: IM |
Affiliation:
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Department of Experimental and Diagnostic Medicine, Section of General Pathology, Interdisciplinary Center for the Study of Inflammation (ICSI), Emilia Romagna Laboratory BioPharmaNet, and Laboratory for Technologies of Advanced Therapies (LTTA) University of Ferrara, Ferrara, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphate
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metabolism Animals Apoptosis* Calcium / metabolism* Calcium Signaling* Cell Line Cell Nucleus / metabolism Cells, Cultured Cytosol / metabolism Endoplasmic Reticulum / metabolism* Homeostasis Humans Inositol 1,4,5-Trisphosphate / metabolism Inositol 1,4,5-Trisphosphate Receptors / metabolism Intracellular Membranes / metabolism Mice Mitochondria / metabolism Nuclear Proteins / genetics, metabolism* Phosphorylation Protein Phosphatase 2 / metabolism Proto-Oncogene Proteins c-akt / metabolism Recombinant Fusion Proteins / metabolism Stress, Physiological Transcription Factors / genetics, metabolism* Tumor Suppressor Proteins / genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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GGP05284//Telethon; K99 CA139009/CA/NCI NIH HHS; K99 CA139009-01A1/CA/NCI NIH HHS; K99 CA139009-02/CA/NCI NIH HHS; R01 CA071692-04S1/CA/NCI NIH HHS; R01 CA102142-07/CA/NCI NIH HHS; R01 CA142874-01/CA/NCI NIH HHS; R01 CA142874-02/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Inositol 1,4,5-Trisphosphate Receptors; 0/Nuclear Proteins; 0/Pml protein, mouse; 0/Recombinant Fusion Proteins; 0/Transcription Factors; 0/Tumor Suppressor Proteins; 56-65-5/Adenosine Triphosphate; 7440-70-2/Calcium; 85166-31-0/Inositol 1,4,5-Trisphosphate; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 3.1.3.16/Protein Phosphatase 2 |
| Comments/Corrections | |
Comment In:
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Dev Cell. 2010 Dec 14;19(6):789-90
[PMID:
21145493
]
Science. 2010 Nov 26;330(6008):1183-4 [PMID: 21109655 ] |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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