PML Regulates Apoptosis at Endoplasmic Reticulum by Modulating Calcium Release

• DOI: 10.1126/science.1189157
• Publication Date: 2010-10-29T04:20:32Z
• Authors: Carlotta Giorgi; Keisuke Ito; Hui-Kuan Lin; Clara Santangelo; Mariusz R. Wiecko...; Magdalena Lebiedz...; Angela Bononi; Massimo Bonora; Jerzy Duszynski; Rosa Bernardi; Rosario Rizzuto; Carlo Tacchetti; Paolo Pinton; Pier Paolo Pandolfi
• Keywords: Calcium Signaling

The promyelocytic leukemia (PML) tumor suppressor is a pleiotropic modulator of apoptosis. However, the molecular basis for such diverse proapoptotic role currently unknown. We show that extranuclear Pml was specifically enriched at endoplasmic reticulum (ER) and mitochondria-associated membranes, signaling domains involved in ER-to-mitochondria calcium ion (Ca(2+)) transport induction found complexes large size with inositol 1,4,5-trisphosphate receptor (IP(3)R), protein kinase Akt, phosphatase 2a (PP2a). essential Akt- PP2a-dependent modulation IP(3)R phosphorylation turn IP(3)R-mediated Ca(2+) release from ER. Our findings provide mechanistic explanation apoptosis identify pharmacological target signals.