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.
Colombo
Riccardo
R
European Institute of Oncology, Department of Experimental Oncology, Via Ripamonti 435, 20141 Milan, Italy.
Boggio
Roberto
R
Seiser
Christian
C
Draetta
Giulio F
GF
Chiocca
Susanna
S
D016475:3T3 Cells; D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D005786:Gene Expression Regulation; D006367:HeLa Cells; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D000071156:Promyelocytic Leukemia Protein; D025842:SUMO-1 Protein / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D014764:Viral Proteins / Q000378:metabolism*; D014779:Virus Replication
C105052:CELO protein, adenovirus; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; D025842:SUMO-1 Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D014764:Viral Proteins; C070576:PML protein, human; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases; D008239:Lysine