PML Regulates Apoptosis at Endoplasmic Reticulum by Modulating Calcium Release
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- 26 November 2010
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 330 (6008), 1247-1251
- https://doi.org/10.1126/science.1189157
Abstract
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 (Ca2+) transport and in induction of apoptosis. We found Pml in complexes of large molecular size with the inositol 1,4,5-trisphosphate receptor (IP3R), protein kinase Akt, and protein phosphatase 2a (PP2a). Pml was essential for Akt- and PP2a-dependent modulation of IP3R phosphorylation and in turn for IP3R-mediated Ca2+ 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 Ca2+ signals.Keywords
This publication has 21 references indexed in Scilit:
- Isolation of mitochondria-associated membranes and mitochondria from animal tissues and cellsNature Protocols, 2009
- Structural and functional link between the mitochondrial network and the endoplasmic reticulumThe International Journal of Biochemistry & Cell Biology, 2009
- MAM: more than just a housekeeperTrends in Cell Biology, 2009
- Akt kinase reducing endoplasmic reticulum Ca2+ release protects cells from Ca2+-dependent apoptotic stimuliBiochemical and Biophysical Research Communications, 2008
- Calcium and apoptosis: ER-mitochondria Ca2+ transfer in the control of apoptosisOncogene, 2008
- Regulation of apoptosis by PML and the PML-NBsOncogene, 2008
- Ca2+ Signaling, Mitochondria and Cell DeathCurrent Molecular Medicine, 2008
- Phosphorylation of inositol 1,4,5-trisphosphate receptors by protein kinase B/Akt inhibits Ca 2+ release and apoptosisProceedings of the National Academy of Sciences of the United States of America, 2008
- Calcium SignalingCell, 2007
- Biosensors for the Detection of Calcium and pHMethods in cell biology, 2007