Interferon-modulated expression of genes encoding the nuclear-dot-associated proteins Sp100 and promyelocytic leukemia protein (PML)

Promyelocytic leukemia protein (PML) and Sp100 are transcription-regulatory proteins which colocalize in discrete nuclear dots and play a role in autoimmunity, oncogenesis and virus-host interaction. Interferons (IFNs) were shown previously to increase strongly the levels of Sp100 mRNA and protein. Here, we examined which mechanisms lead to upregulation of Sp100 gene expression and whether IFN's also increase expression of the promyelocytic leukemia (PML) gene, We found that both mRNA and protein levels of PML are also strongly upregulated by IFN's. In addition, new Sp100 and PML proteins were detected immunologically after IFN treatment of cells. Nuclear run-on analysis revealed protein-synthesis-independent, rapid IFN-enhanced transcription rates as well as synergistic activation of the Sp100 and PML genes by type-I and type-II IFNs. These data demonstrate that PML and Sp100 belong to the growing family of IFN-stimulated genes (ISGs) upregulated most likely by the transcription factor ISGF3, and indicate that IFNs also qualitatively alter the expression of these two genes.