Interferon-stimulated gene 20 kDa protein (ISG20)

Interferon-stimulated gene 20 kDa protein (ISG20) is an interferon-induced exonuclease that preferentially cleaves single-stranded RNA over DNA, with broad antiviral properties[2][3][4][5][8]. ISG20 is categorized in the DEDDh exonuclease family and functions principally as part of the innate immune response, degrading viral RNA and sometimes DNA, directly restricting the replication of a wide range of viruses. Recent research demonstrates that ISG20 also inhibits translation of 'non-self' (exogenous) genetic material, acting not solely via degradation but also by translational repression[5]. ISG20 is also implicated in tumor progression, cell cycle regulation, and metastasis, particularly in renal cell carcinoma[7]. Expression is upregulated in response to interferon signaling and may serve as a susceptibility or progression biomarker in infection, cancer, and inflammation. Its catalytic activity depends on several key residues and manganese as a co-factor[3][8]. While considered a promising target for antivirals and cancer therapeutics, the full scope of its mechanisms is not completely understood, and safety concerns center on its potential broad impact on RNA metabolism and cell function if therapeutically manipulated[5].

Other names

ISG20HeLa estrogen-modulated, band 45 (HEM45)Estrogen-regulated transcript 45 proteinInterferon-stimulated exonuclease gene 20Promyelocytic leukemia nuclear body-associated protein ISG20

For interferon therapies: induction/upregulation of ISG20 expression to enhance antiviral defenses. For future drugs: modulating ISG20 activity to control viral RNA degradation or influence cell cycle/cancer phenotypes (conceptual, not established).