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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.