Apoptosis

, Volume 13, Issue 4, pp 562–572

Mitochondrial localization and pro-apoptotic effects of the interferon-inducible protein ISG12a

Original Paper

DOI: 10.1007/s10495-008-0190-0

Cite this article as:
Rosebeck, S. & Leaman, D.W. Apoptosis (2008) 13: 562. doi:10.1007/s10495-008-0190-0

Abstract

ISG12a is one of the most highly induced genes following treatment of cells with type I interferons (IFNs). The encoded protein belongs to a family of poorly characterized, low molecular weight IFN-inducible proteins that includes 6–16 (G1P3), 1–8U (IFITM3), and 1–8D (IFITM2). Our studies demonstrate that the ISG12a protein associates with or inserts into the mitochondrial membrane. Transient expression of ISG12a led to decreased viable cell numbers and enhanced sensitivity to DNA-damage induced apoptosis, effects that were blocked by Bcl-2 co-expression or treatment with a pan-caspase inhibitor. ISG12a enhanced etoposide induced cytochrome c release, Bax activation and loss of mitochondrial membrane potential. siRNA-mediated inhibition of ectopic ISG12a protein expression prevented the sensitization to etoposide-induced apoptosis and also decreased the ability of IFN-β pretreatment to sensitize cells to etoposide, thereby demonstrating a role for ISG12a in this process. These data suggest that ISG12a contributes to IFN-dependent perturbation of normal mitochondrial function, thus adding ISG12a to a growing list of IFN-induced proteins that impact cellular apoptosis.

Keywords

Apoptosis Caspases Membrane potential Bcl-2 Bax 

Abbreviations

IFITM

IFN inducible transmembrane protein

IFN

Interferon

ISG

IFN-stimulated gene

Mtch

Mitochondrial carrier homolog

PVDF

Polyvinylidene difluoride

SP

Signal peptide

TRAIL

Tumor necrosis factor related apoptosis inducing ligand

aa

Amino acid

COX IV

Cytochrome oxidase subunit IV

Supplementary material

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  1. 1.Department of Biological SciencesThe University of ToledoToledoUSA

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