| First Author | Giorgi C | Year | 2010 |
| Journal | Science | Volume | 330 |
| Issue | 6008 | Pages | 1247-51 |
| PubMed ID | 21030605 | Mgi Jnum | J:166717 |
| Mgi Id | MGI:4849347 | Doi | 10.1126/science.1189157 |
| Citation | Giorgi C, et al. (2010) PML regulates apoptosis at endoplasmic reticulum by modulating calcium release. Science 330(6008):1247-51 |
| abstractText | 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. |
