Sept4/ARTS is required for stem cell apoptosis and tumor suppression

被引：71

作者：

Garcia-Fernandez, Maria ^{[1
]}

Kissel, Holger ^{[1
]}

Brown, Samara ^{[1
]}

Gorenc, Travis ^{[1
]}

Schile, Andrew J. ^{[1
]}

Rafii, Shahin ^{[2
]}

Larisch, Sarit ^{[3
]}

Steller, Hermann ^{[1
]}

机构：

[1] Rockefeller Univ, Howard Hughes Med Inst, Lab Apoptosis & Canc Biol, New York, NY 10065 USA

[2] Cornell Univ, Weill Med Coll, Howard Hughes Med Inst, New York, NY 10021 USA

[3] Univ Haifa, Dept Biol, Cell Death Res Lab, IL-31905 Haifa, Israel

来源：

GENES & DEVELOPMENT | 2010年 / 24卷 / 20期

关键词：

Apoptosis; cancer; tumor suppressor; IAP; stem cells; lymphoma; SEPTIN GENE FAMILY; TRANSGENIC MICE; C-MYC; TARGETED THERAPIES; LIGASE ACTIVITY; DEFICIENT MICE; ARTS PROTEIN; CANCER; DEATH; DROSOPHILA;

D O I：

10.1101/gad.1970110

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Inhibitor of Apoptosis Proteins (IAPs) are frequently overexpressed in tumors and have become promising targets for developing anti-cancer drugs. IAPs can be inhibited by natural antagonists, but a physiological requirement of mammalian IAP antagonists remains to be established. Here we show that deletion of the mouse Sept4 gene, which encodes the IAP antagonist ARTS, promotes tumor development. Sept4-null mice have increased numbers of hematopoietic stem and progenitor cells, elevated XIAP protein, increased resistance to cell death, and accelerated tumor development in an E mu-Myc background. These phenotypes are partially suppressed by inactivation of XIAP. Our results suggest that apoptosis plays an important role as a frontline defense against cancer by restricting the number of normal stem cells.

引用

页码：2282 / 2293

页数：12

共 68 条

[1] Evidence for functional differentiation among Drosophila septins in cytokinesis and cellularization [J].

Adam, JC ;

Pringle, JR ;

Peifer, M .

MOLECULAR BIOLOGY OF THE CELL, 2000, 11 (09) :3123-3135

[2] THE C-MYC ONCOGENE DRIVEN BY IMMUNOGLOBULIN ENHANCERS INDUCES LYMPHOID MALIGNANCY IN TRANSGENIC MICE [J].

ADAMS, JM ;

HARRIS, AW ;

PINKERT, CA ;

CORCORAN, LM ;

ALEXANDER, WS ;

CORY, S ;

PALMITER, RD ;

BRINSTER, RL .

NATURE, 1985, 318 (6046) :533-538

[3] Structural insights shed light onto septin assemblies and function [J].

Barral, Yves ;

Kinoshita, Makoto .

CURRENT OPINION IN CELL BIOLOGY, 2008, 20 (01) :12-18

[4] APOPTOTIC CELL-DEATH INDUCED BY C-MYC IS INHIBITED BY BCL-2 [J].

BISSONNETTE, RP ;

ECHEVERRI, F ;

MAHBOUBI, A ;

GREEN, DR .

NATURE, 1992, 359 (6395) :552-554

[5] Stem cells and cancer: Two faces of eve [J].

Clarke, MF ;

Fuller, M .

CELL, 2006, 124 (06) :1111-1115

[6] STE20-LIKE PROTEIN-KINASES ARE REQUIRED FOR NORMAL LOCALIZATION OF CELL-GROWTH AND FOR CYTOKINESIS IN BUDDING YEAST [J].

CVRCKOVA, F ;

DEVIRGILIO, C ;

MANSER, E ;

PRINGLE, JR ;

NASMYTH, K .

GENES & DEVELOPMENT, 1995, 9 (15) :1817-1830

[7] Cell death: Critical control points [J].

Danial, NN ;

Korsmeyer, SJ .

CELL, 2004, 116 (02) :205-219

[8] A mouse model system to genetically dissect the molecular mechanisms regulating tumorigenesis [J].

Degenhardt, Kurt ;

White, Eileen .

CLINICAL CANCER RESEARCH, 2006, 12 (18) :5298-5304

[9] The role of apoptosis in the regulation of hematopoietic stem cells:: Overexpression of BCL-2 increases both their number and repopulation potential [J].

Domen, J ;

Cheshier, SH ;

Weissman, IL .

JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 191 (02) :253-263

[10] Increased sensitivity to apoptotic stimuli in c-abl-deficient progenitor B-cell lines [J].

Dorsch, M ;

Goff, SP .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (23) :13131-13136

← 1 2 3 4 5 6 7 →