The adenovirus protein Gam1 interferes with sumoylation of histone deacetylase 1

The adenovirus early gene product Gam1 is crucial for virus replication and induces certain cellular genes by inactivating histone deacetylase 1 (HDAC1). We demonstrate that Gam1 (i) destroys promyelocitic leukemia nuclear bodies, (ii) delocalizes SUMO-1 into the cytoplasm and (iii) influences the SUMO-1 pathway. In addition, we show that Gam1 counteracts HDAC1 sumoylation both in vivo and in vitro. Sumoylation of HDAC1 does not seem to be absolutely required for HDAC1 biological activity but is part of a complex regulatory circuit that also includes phosphorylation of the deacetylase. Our data demonstrate that Gam1 is a viral protein that can affect simultaneously two signaling pathways: sumoylation and acetylation.