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C2a: 2009, September 22-26, RUBICON and EMBO Conference: Ubiquitin and Ubiquitin-like Modifiers in Health and Disease, Riva del Garda, Italy
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This was the second time for this EMBO meeting to be held in Riva del Garda. The close vicinity of the Garda lake and the impressive view of the Italian Alps already made the meeting a success. Luckily also the quality of the talks and the amount o unpublished data in both the talks and the posters was excellent. The total number of participants was 226 (90 female and 136 male).
The meeting started with four talks addressing the resent discoveries in proteasome assembly and the chaperones that assist this assembly, thereby overcoming the problems that arise during the assembly of this gigantic complex machinery. Although the meeting covered a wide variety of facets within the ubiquitin family it became clear that more and more labs are addressing the intriguing function of Cdc48/p97 in the ubiquitin proteasome system. Perhaps reflecting the essential part it plays in many pathways and the elegant way it functions by using a wide variety of cofactors with seemingly opposing activities (maybe reminding of the 19S cap). Elegant C. elegans work revealed an unknown role of cdc48/p97 in ageing. Especially intriguing since a combinational mutant of partial Cdc48/p97 knockdown and a cofactor of Cdc48/p97 extends lifespan and this depends on the insulin/IGF axis. Also the work on mitosis and Cdc48/p97 mediated auroraB extraction from chromatin makes clear that more and more pathways are clients of the Cdc48/p97 machinery. Besides novel functions also insight in cofactor (for example Ufd2) binding was given. Even in the more classical function of Cdc48/p97, namely ERAD, an overwhelming amount of data was presented covering new cofactors, sub-pathways and even the entire interactome of human ERAD.
A brief session gave a nice overview of DNA repair pathways that are controlled by ubiquitin (interstrand crosslink repair) or ubiquitin and SUMO (lesion or gap repair during DNA synthesis). A complex interplay of recombination, polyubiquitylation of PCNA and SUMOylation at stalled forks is essential for progression of replication, with a previous unappreciated role for the structural maintenance of chromosomes proteins 5 and 6 (related to the cohesion and condensin proteins).
Concerning the ubiquitin-like modifiers, an update on NEDDylation in SCF regulation and more specifically possible new components in Rtt101 NEDDylation, the TFIIH component Tfb3, was given. The progress on the new bacterial ubiquitin-like modifier, Pup, as a promising drug target for tuberculosis underscored the direct implications for human health of fundamental research.
The multitude of possibilities and complexities in the regulation of protein function created by posttranslational protein-modifications was elegantly shown. For example crosstalk of ubiquitin and ubiquitin-like modifiers in autophagy, phosphorylation of SUMO interactive motives, polyubiquitylation (versus monoubiquitylation) as determined by cis-trans proline isomerization or the difference of K63 and linear ubiquitylation in NFkB signaling all show that most pathways are regulated at different levels. Moreover it became evidently clear that the events (most often the different protein modifications) that direct the outcome of these pathways are in turn influenced by complex control mechanisms as well. As closure an impressive overview of the interactome of deubiquitylation enzymes (the canonical way of regulating ubiquitylation events) was shown. Perhaps revealing a tip of the iceberg of the total regulatory connections of ubiquitylation (and ubiquitin-like modifications) and the difficult task that awaits in the future of putting these into the right biological context.
Invited Speakers
Jeff Brodsky
Aaron Ciechanover
Allan D’Andrea
Heran Darwin
Ray Deshaies
Paolo diFiore
Ivan Dikic
Dan Finley
Wade Harper
Mark Hochstrasser
Stefan Jentsch
Ron Kopito
Chris Lima
Maria Masucci
Frauke Melchior
Michele Pagano
Matthias Peter
Simona Polo
Michael Rape
Hermann Schindelin
Brenda Schulman
Keiji Tanaka
Mike Tyers
Helle Ulrich
Sylvie Urbe
Yosef Yarden
Allan Weissman
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Thomas Sommer (Principal Investigator / Thomas Sommer's Group)
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