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

María García-Fernández; Holger Kissel; Samara Brown; Travis Gorenc; Andrew J. Schile; Shahin Rafii; Sarit Larisch; Hermann Steller

doi:10.1101/gad.1970110

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

María García-Fernández, Holger Kissel, Samara Brown, Travis Gorenc, Andrew J. Schile, Shahin Rafii, Sarit Larisch, Hermann Steller

Research output: Contribution to journal › Article › peer-review

Abstract

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 Em-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.

Original language	English
Pages (from-to)	2282-2293
Number of pages	12
Journal	Genes and Development
Volume	24
Issue number	20
DOIs	https://doi.org/10.1101/gad.1970110
State	Published - 15 Oct 2010

Keywords

Apoptosis
Cancer
IAP
Lymphoma
Stem cells
Tumor suppressor

ASJC Scopus subject areas

General Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1101/gad.1970110

Cite this

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title = "Sept4/ARTS is required for stem cell apoptosis and tumor suppression",

abstract = "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 Em-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.",

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T1 - Sept4/ARTS is required for stem cell apoptosis and tumor suppression

AU - García-Fernández, María

AU - Kissel, Holger

AU - Brown, Samara

AU - Gorenc, Travis

AU - Schile, Andrew J.

AU - Rafii, Shahin

AU - Larisch, Sarit

AU - Steller, Hermann

PY - 2010/10/15

Y1 - 2010/10/15

N2 - 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 Em-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.

AB - 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 Em-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.

KW - Apoptosis

KW - Cancer

KW - IAP

KW - Lymphoma

KW - Stem cells

KW - Tumor suppressor

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U2 - 10.1101/gad.1970110

DO - 10.1101/gad.1970110

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SN - 0890-9369

VL - 24

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EP - 2293

JO - Genes and Development

JF - Genes and Development

IS - 20

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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