Promyelocytic leukemia zinc finger protein regulates interferon-mediated innate immunity

Dakang Xu, Michelle Holko, Anthony John Sadler, Bernadette Maree Scott, Shigeki Higashiyama, Windy Berkofsky-Fessler, Melanie J McConnell, Pier Paolo Pandolfi, Jonathan D Licht, Bryan Raymond George Williams

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71 Citations (Scopus)


Interferons (IFNs) direct innate and acquired immune responses and, accordingly, are used therapeutically to treat a number of diseases, yet the diverse effects they elicit are not fully understood. Here, we identified the promyelocytic leukemia zinc finger (PLZF) protein as a previously unrecognized component of the IFN response. IFN stimulated an association of PLZF with promyelocytic leukemia protein (PML) and histone deacetylase 1 (HDAC1) to induce a decisive subset of IFN-stimulated genes (ISGs). Consequently, PLZF-deficient mice had a specific ISG expression defect and as a result were more susceptible to viral infection. This susceptibility correlated with a marked decrease in the expression of the key antiviral mediators and an impaired IFN-mediated induction of natural killer cell function. These results provide new insights into the regulatory mechanisms of IFN signaling and the induction of innate antiviral immunity.
Original languageEnglish
Pages (from-to)802 - 816
Number of pages15
Issue number6
Publication statusPublished - 2009

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