Viral control of the SUMO pathway: Gam1, a model system.
SUMO (small ubiquitin-related modifier) is a ubiquitin-like family member that is conjugated to its substrates through discrete enzymatic steps: activation, involving the E1 enzyme [SAE (SUMO-activating enzyme) 1-SAE2], conjugation, involving the E2 enzyme [Ubc9 (ubiquitin-conjugating enzyme 9)], and substrate modification, through the co-operation of Ubc9 and E3 protein ligases. Work from our laboratory has shown the first example of a viral protein, Gam1, that binds to the E1 heterodimer, inhibiting its function and causing a complete block of the SUMOylation pathway both in vivo and in vitro, followed by SAE1-SAE2 degradation. The mechanism by which a viral protein inactivates and subsequently degrades an essential cellular enzyme, arresting a key regulatory pathway, will be discussed. Although four distinct SUMO isoforms have been described, I will use SUMO to describe the entire system.
Chiocca
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Department of Experimental Oncology, European Institute of Oncology, Milan, Italy. chiocca@ifom-ieo-campus.it
D000256:Adenoviridae / Q000378:metabolism; D000818:Animals; D007976:Leupeptins / Q000494:pharmacology; D008954:Models, Biological; D025841:Small Ubiquitin-Related Modifier Proteins / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000378:metabolism; D014764:Viral Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*
C105052:CELO protein, adenovirus; D007976:Leupeptins; D025841:Small Ubiquitin-Related Modifier Proteins; D014764:Viral Proteins; D044767:Ubiquitin-Protein Ligases; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde