INTERFERON-ALPHA INDUCTION OF PML NUCLEAR BODIES IS INHIBITED BY TRICHOSTATIN A
Vlasakova J., Hodny Z., and Hozak P.
Department of Cell Ultrastructure and Molecular Biology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic The nucleus of the eukaryotic cell is a complex organelle compartmentalized into structural and functional domains. One of these nuclear domains are matrix-associated multi-protein complexes, promyeolocytic leukemia nuclear bodies (PML NBs). The gene product, PML protein, is essential for proper formation and integrity of PML NBs. Although the biochemical function of PML and PML NBs remain still unclear, there is an evidence for its contribution in response to a variety of cell states like in cancer, apoptosis, and viral infection. It is known that type I and II interferons (IFNs) dramatically increase the transcription of the PML gene through an IFN-stimulated response element present in the PML gene promoter. Additionally, IFNs increases expression of other structural components of PML NBs - Sp100 and ISG20. This can contribute to the observed increase in the number of PML NBs. In this study we have shown that the cell response to interferon is strongly reduced in cells treated with trichostatin A, an inhibitor of protein deacetylases. This indicates that the protein hyperacetylation interferes with some stage of PML NBs assembly. The effect of trichostatin A on the expression of structural components of PML NBs and de novo formation of PML NBs after their dispersion by Cd2+ ions or by heat shock is also presented.
