Apoptotic properties of the type 1 interferon induced family of mitochondrial membrane ISG12 proteins

– novel members of the BH3-only-like family of proteins

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Abstract:

Interferons (IFNs) are a family of cytokines with growth inhibitory, and antiviral functions. Human IFNs are grouped into type 1 and type 2, and the biological actions of IFNs are mainly mediated through the gene products of more than 300 IFN stimulated genes (ISGs). The ISG12 family of proteins consists of ISG12A, ISG12B, ISG12C and ISG 6–16, a group of small type 1 IFN induced membrane proteins. Due to an alternative splicing event and a gene variation, four variants of the ISG12A protein exists. We have expressed the ISG12 proteins transiently in HEK 293 cells FLAG-tagged in either the C-terminal or N-terminal ends. We have also isolated HEK293 GeneSwitch inducible cell lines expressing the four variants of un-tagged ISG12A proteins.

We will present data showing that the ISG12A variants, as well as ISG12B and ISG12C either induce apoptosis directly, or prime the cells for apoptosis by the apoptosis inducers gossypol and TNFα. In contrast 6–16 do not have the same apoptotic properties as the other members of the ISG12 family of proteins. We will also present electron microscopy data showing that these proteins are localized in the mitochondrial membrane. Thus the apoptotic properties of this ISG12 family of type 1 IFN induced proteins most likely occur in the mitochondria permeabilization process during apoptosis. This suggestion is further supported by the finding of a putative Bcl-2 homology (BH)-3 motif in the sequences of the ISG12 proteins. Collectively, these findings indicate that the ISG12 proteins are members of a novel BH3-only-like family of proteins.

Document Type: Abstract

DOI: http://dx.doi.org/10.1111/j.1600-0463.2008.001165_51.x

Affiliations: 1: Molekylærbiologisk Institut, Aarhus Universitet, C. F. Møllers Alle 1130, 8000 Århus C 2: UQ Diamantina Institute for Cancer, Immunology and Metabolic Medicine, The University of Queensland, Brisbane, QLD 4072. Australia 3: Cellebiologisk afd., Anatomisk Institut, Wilhelm Meyers Alle 1234, Aarhus Universitet, 8000 Århus C

Publication date: May 1, 2008

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