期刊
SCIENCE
卷 330, 期 6008, 页码 1247-1251出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1189157
关键词
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资金
- National Cancer Institute
- NIH
- AIRC
- FISM
- Telethon
- Ministry of Health
- PRIN
- FP7 MyoAGE
- Cariparo Foundation
- Ministry of Science and Higher Education in Poland
- Polish Mitochondrial Network
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.
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