INDUCTION OF THE PML PROTEIN BY INTERFERONS IN NORMAL AND APL CELLS

PML has been identified through its fusion to the RAR alpha gene in ac ute promyelocytic leukemia (APL). The PML protein is specifically asso ciated to nuclear bodies (NBs) whose alterations in APL were proposed to contribute to leukemogenesis. The role of this nuclear domain (whic h also harbors the Sp100 autoantigen and the NDP52 protein) is unknown . Here, we show that the PML protein, like Sp100 and NDP52, is induced by interferons (IFNs alpha, beta and gamma) in a large variety of hum an cells. Interestingly, the NBs that contain the three IFN-induced pr oteins appear to be associated to speckles labelled by the IFN-mediato r Mx1. These observations link NBs to IFN response pathways, which may contribute to the elucidation of the biological role of these structu res. In APL cells, IFNs induced both PML and PML/RAR alpha expression, resulting in an increased sequestration of PML and RXRs in the micros peckles induced by the fusion protein. As PML has growth suppressing p roperties, it may mediate some of the antiproliferative effects of IFN . In APL, inactivation of PML may result in disruption of growth contr ol.