Gam1 and the SUMO pathway.
Post-translational modifications of proteins have critical roles in many cellular processes because they can cause rapid changes in the functions of preexisting proteins, multiprotein complexes and subcellular structures. Sumoylation, a ubiquitin-like dynamic and reversible post-translational modification system, is an enzymatic cascade leading to the covalent attachment of SUMO to it target proteins. This modification involves three steps and different enzymes: SUMO-activating enzyme E1 (SAE1/SAE2), SUMO-conjugating enzyme E2 (UBC9), SUMO ligases E3s, and SUMO cleaving enzymes. Although the identification of SUMO-modified substrates has progressed rapidly, the biological function of SUMO and regulation of SUMO conjugation are still not well understood. Some viral proteins have been identified as substrates for SUMO modification as well as altering the sumoylation status of host cell proteins. We have been studying an unusual adenoviral protein, Gam1, a strong and global transcriptional activator of both viral and cellular genes that inactivates HDAC1. We have recently expanded the known functions of Gam1 by demonstrating that Gam1 also inhibits the SUMO pathway by interfering with the activity of E1 heterodimer (SAE1/SAE2), leading to the accumulation of SUMO-unmodified substrates. Our data provides a clear example of the effects of a viral infection on host sumoylation and supports the idea that viruses have multifunctional protein that can target essential biochemical pathways.
Boggio
Roberto
R
Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
Chiocca
Susanna
S
D000251:Adenosine Triphosphatases; D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D020816:Amino Acid Motifs; D000818:Animals; D002453:Cell Cycle; D004268:DNA-Binding Proteins / Q000502:physiology*; D019281:Dimerization; D015966:Gene Expression Regulation, Fungal; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D025842:SUMO-1 Protein / Q000737:chemistry*; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D025842:SUMO-1 Protein; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D000251:Adenosine Triphosphatases; C499333:SNF2 protein, S cerevisiae