Journal article
Nuclear Receptor SHP, a Death Receptor That Targets Mitochondria, Induces Apoptosis and Inhibits Tumor Growth
Molecular and cellular biology, Vol.30(6), pp.1341-1356
03/15/2010
DOI: 10.1128/MCB.01076-09
PMCID: PMC2832505
PMID: 20065042
Abstract
ABSTRACT Small heterodimer partner (SHP) is an epigenetically regulated nuclear transcriptional repressor that suppresses the development of liver cancer by inhibiting cellular growth. Here we report a novel cytoplasmic function of SHP through its regulation of mitochondrial activity. SHP is a pivotal cell death receptor that targets mitochondria, where it binds with Bcl-2, disrupts Bcl-2/Bid interaction, and induces cytochrome c release. The apoptosis inducer AHPN {retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid} acts by regulating SHP gene expression and promotes the translocation of SHP from the nucleus to the mitochondria. Induction of apoptosis by SHP activation inhibits peritoneal pancreatic tumor growth. Our findings provide for the first time a mechanism by which SHP regulates cell survival, namely, by controlling mitochondrial function via modulating the activity of Bcl-2 through AHPN-mediated or AHPN-independent action. Thus, SHP regulates a mechanism by which apoptotic signals can mediate local control of mitochondrial function and apoptosis, which in turn may limit tumorigenesis.
Details
- Title: Subtitle
- Nuclear Receptor SHP, a Death Receptor That Targets Mitochondria, Induces Apoptosis and Inhibits Tumor Growth
- Creators
- Yuxia Zhang - Departments of Medicine and Oncological Sciences and Huntsman Cancer InstituteJamie Soto - Division of Endocrinology, Metabolism and Diabetes and Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, Utah 84132Kyungtae Park - Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas 66160Gunda Viswanath - Departments of Medicine and Oncological Sciences and Huntsman Cancer InstituteScott Kuwada - Departments of Medicine and Oncological Sciences and Huntsman Cancer InstituteE. Dale Abel - Division of Endocrinology, Metabolism and Diabetes and Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, Utah 84132Li Wang - Departments of Medicine and Oncological Sciences and Huntsman Cancer Institute
- Resource Type
- Journal article
- Publication Details
- Molecular and cellular biology, Vol.30(6), pp.1341-1356
- DOI
- 10.1128/MCB.01076-09
- PMID
- 20065042
- PMCID
- PMC2832505
- NLM abbreviation
- Mol Cell Biol
- ISSN
- 0270-7306
- eISSN
- 1098-5549
- Language
- English
- Date published
- 03/15/2010
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984025297002771
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