Sept4/ARTS is Required for Stem Cell Apoptosis and Tumor Suppression

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2010 Oct 19

PMID 20952537

Citations 42

Authors

Maria Garcia-Fernandez

Holger Kissel

Samara Brown

Travis Gorenc

Andrew J Schile

Shahin Rafii

Sarit Larisch

Hermann Steller

Affiliations

Soon will be listed here.

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 Eμ-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.

Citing Articles

ARTS and small-molecule ARTS mimetics upregulate p53 levels by promoting the degradation of XIAP.

Abbas R, Hartmann O, Asiss D, Abbas R, Kagan J, Kim H Apoptosis. 2024; 29(7-8):1145-1160.

PMID: 38684550 PMC: 11263447. DOI: 10.1007/s10495-024-01957-2.

Unearthing the role of septins in viral infections.

Khairat J, Hatta M, Abdullah N, Azman A, Calvin S, Hassan S Biosci Rep. 2024; 44(3).

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Winkler R, Piskor E, Kosan C Cells. 2023; 12(1).

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The ARTS of p53-dependent mitochondrial apoptosis.

Hao Q, Chen J, Lu H, Zhou X J Mol Cell Biol. 2022; 14(10).

PMID: 36565718 PMC: 10053023. DOI: 10.1093/jmcb/mjac074.

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