PML Regulates Apoptosis at Endoplasmic Reticulum by Modulating Calcium Release

被引：338

作者：

Giorgi, Carlotta ^{[1
,2
,3
,4
,5
,6
,7
]}

Ito, Keisuke ^{[5
,6
,7
]}

Lin, Hui-Kuan ^{[7
]}

Santangelo, Clara ^{[8
,9
]}

Wieckowski, Mariusz R. ^{[10
]}

Lebiedzinska, Magdalena ^{[10
]}

Bononi, Angela ^{[1
,2
]}

Bonora, Massimo ^{[1
,2
]}

Duszynski, Jerzy ^{[10
]}

Bernardi, Rosa ^{[5
,6
,7
,11
]}

Rizzuto, Rosario ^{[12
]}

Tacchetti, Carlo ^{[8
,9
,13
]}

Pinton, Paolo ^{[1
,2
,5
,6
,7
]}

Pandolfi, Pier Paolo ^{[5
,6
,7
]}

机构：

[1] Univ Ferrara, Emilia Romagna Lab BioPharmaNet, Dept Expt & Diagnost Med, Sect Gen Pathol,ICSI, I-44100 Ferrara, Italy

[2] Univ Ferrara, Lab Technol Adv Therapies, I-44100 Ferrara, Italy

[3] Univ Vita Salute San Raffaele, Ctr Excellence Cell Dev, Milan, Italy

[4] IIT Network, Res Unit Mol Neurosci, Milan, Italy

[5] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr,Dept Med, Beth Israel Deaconess Canc Ctr,Canc Genet Program, Boston, MA 02215 USA

[6] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr,Dept Pathol, Beth Israel Deaconess Canc Ctr,Canc Genet Program, Boston, MA 02215 USA

[7] Mem Sloan Kettering Canc Ctr, Dept Pathol, Canc Biol & Genet Program, New York, NY 10065 USA

[8] Univ Genoa, Ctr Cell Oncol, IFOM FIRC Inst Mol Oncol Fdn, Genoa, Italy

[9] Univ Genoa, Dept Expt Med, Ultrastruct MicroSCoBiO Res Ctr, Genoa, Italy

[10] M Nencki Inst Expt Biol, PL-02093 Warsaw, Poland

[11] San Raffaele Res Inst, Dept Mol Oncol, Milan, Italy

[12] Univ Padua, Dept Biomed Sci, Padua, Italy

[13] Ist Sci San Raffaele, Expt Imaging Ctr, I-20132 Milan, Italy

来源：

SCIENCE | 2010年 / 330卷 / 6008期

关键词：

CA2+ RELEASE; MITOCHONDRIA; BCL-2; CELLS;

D O I：

10.1126/science.1189157

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：1247 / 1251

页数：5

共 21 条

[1] Regulation of apoptosis by PML and the PML-NBs
Bernardi, R.
Papa, A.
Pandolfi, P. P.
[J]. ONCOGENE, 2008, 27 (48) : 6299 - 6312
[2] Calcium signaling
Clapham, David E.
[J]. CELL, 2007, 131 (06) : 1047 - 1058
[3] Characterization of endogenous human promyelocytic leukemia isoforms
Condemine, Wilfried
Takahashi, Yuki
Zhu, Jun
Puvion-Dutilleul, Francine
Guegan, Sarah
Janin, Anne
de The, Hugues
[J]. CANCER RESEARCH, 2006, 66 (12) : 6192 - 6198
[4] Giorgi C, 2008, CURR MOL MED, V8, P119
[5] Structural and functional link between the mitochondrial network and the endoplasmic reticulum
Giorgi, Carlotta
De Stefani, Diego
Bononi, Angela
Rizzuto, Rosario
Pinton, Paolo
[J]. INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2009, 41 (10) : 1817 - 1827
[6] Loss of the tumor suppressor PML in human cancers of multiple histologic origins
Gurrieri, C
Capodieci, P
Bernardi, R
Scaglioni, PP
Nafa, K
Rush, LJ
Verbel, DA
Cordon-Cardo, C
Pandoli, PP
[J]. JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2004, 96 (04): : 269 - 279
[7] MAM: more than just a housekeeper
Hayashi, Teruo
Rizzuto, Rosario
Hajnoczky, Gyorgy
Su, Tsung-Ping
[J]. TRENDS IN CELL BIOLOGY, 2009, 19 (02) : 81 - 88
[8] Cytoplasmic PML function in TGF-β signalling
Lin, HK
Bergmann, S
Pandolfi, PP
[J]. NATURE, 2004, 431 (7005) : 205 - 211
[9] Akt kinase reducing endoplasmic reticulum Ca2+ release protects cells from Ca2+-dependent apoptotic stimuli
Marchi, Saverio
Rimessi, Alessandro
Giorgi, Carlotta
Baldini, Claudio
Ferroni, Letizia
Rizzuto, Rosario
Pinton, Paolo
[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2008, 375 (04) : 501 - 505
[10] The type III inositol 1,4,5-trisphosphate receptor preferentially transmits apoptotic Ca2+ signals into mitochondria
Mendes, CCP
Gomes, DA
Thompson, M
Souto, NC
Goes, TS
Goes, AM
Rodrigues, MA
Gomez, MV
Nathanson, MH
Leite, MF
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (49) : 40892 - 40900

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