ISG20


Interferon-stimulated gene 20 kDa protein is a protein that in humans is encoded by the ISG20 gene. It belongs to the ISG family of proteins, which are typically stimulated by type I interferon as a response to viral infection.

Discovery

ISG20 was discovered in 1997 at the Institute for Molecular Genetics within the University of Montpellier. The new protein was discovered through differential display in IFNα/β treated human cells.
Later it was showed that ISG20 expression is driven directly by ssDNA and ssRNA signalling through NF-kB pathways, leading to a more robust expression of ISG20, than through the interferon pathway.

Structure

ISG20 is classified as a member of the DEDDh exonuclease family, defined by a conserved catalytic core consisting of three aspartate residues and one glutamate residue distributed across the Exo I–III motifs, together with an additional conserved histidine residue essential for activity.

Function

ISG20 is an RNA exonuclease, which under normal physiological conditions contributes to the antiviral response of the host. It belongs to the Rex4 exonucleases subfamily and is evolutionarily related to yeast REXO4.
It is enzymatically capable of degrading single-stranded RNA and single-stranded DNA alike.

Clinical significance

ISG20 shows somewhat opposing activity in different types of cancers. While it drives cell proliferation in breast cancer, AML, glioma, cervical cancer, renal cancer, liver cancer and oral cancer, it has been shown to inhibit cell proliferation in ovarian cancer.
While the pathophysiological mechanism is not fully understood, it is thought that in the majority of cases where ISG20 has a proliferative effect, thyroid hormone stimulation causes the secretion of ISG20, which in turn contributes to proliferation, stimulates migration and drives angiogenesis. The proliferative effect is mediated via metalloproteinase MMP-9 pathway by accelerating the G1/S transition, while the stimulation of expression of extracellular matrix degrading enzymes drives migration and invasion. Angiogenesis is mediated by Interleukin 8 and the JAK/STAT Pathway.