What is Zomes? History and Major Achievements
The biannual Zomes conference series was initiated as a grassroots initiative of scientists studying three related protein complexes, the 19S proteasome, the COP9 signalosome, and the translation initiation factor eIF3 (aka PCI complexes, the “Zomes”). ZOMES I, held in Israel in 1999, brought together, for the first time, researchers from different fields with common interests in these protein complexes of seemingly unrelated cellular functions. This included scientists working on plant development, mammalian cell signaling, yeast and mammalian cell cycle, the ubiquitin-proteasome pathway, and the cellular protein synthesis machinery. One tangible outcome of this meeting was the unified nomenclature of the COP9 signalosome . ZOMES II was held in 2002 in Antalya, Turkey, while ZOMES III met in Berlin, Germany in 2004 . Zomes IV took place in New Haven/Yale . The conference then moved to Yokohama, Japan, in 2008 (Zomes V, ), back to Israel in 2010 (Zomes VI, Safed), and on to Munich, Germany in 2012 (Zomes VII). In 2014, the conference took place in Xiamen, China (Zomes VIII), and in 2017 in Rome, Italy (Zomes IX).
The most important outcome of the Zomes series has been the early and continued realization that the three PCI complexes are not only related structurally but also intimately connected in function. For example, the three complexes share common subunits [5, 6] and even form supercomplexes [7–10]. Secondly, the recognition that cullin-ubiquitin ligases are regulated by CSN-mediated deneddylation – a finding first presented at Zomes III – has had a lasting impact on the proteolysis field. Just to mention two more examples- the molecular architecture of the proteasome and the crystal structure of the COP9 signalosome were reported in Zomes VII and VIII [11-13]. In Zomes VIII we discussed the use of system dynamics and bioinformatics in the study of these molecular complexes, and Zomes IX focus on “Zomes” and ubiquitin in the regulation of protein homeostasis [14-16]. Much remains to be learned about how “Zomes” integrate the control of protein synthesis and degradation upstream and downstream of ZOMES activity: Zomes X will continue to provide an efficient platform for scientific exchange at the forefront of this field and will focus on the mutual links between ZOMES, ubiquitin/ubiquitin-like proteins and protein degradation mechanisms in health and disease, as outlined in the following pages. We expect Zomes X to be particularly exciting, given the new insights on Zomes function and interactions recently published [17-19].
Zomes conferences are unique in several ways:
- A not-for-profit conference by scientists for scientists
- Long history of first disclosures of key findings on functional and physical interactions between PCI complexes
- Interdisciplinary: Diverse organisms are represented (plants, mammals, yeasts, flies, worms)
- Dynamic: An active effort is made at each Zomes conference to attract attendants that newly joined the field
- Interactive: Zomes conferences are small (~150 – 200) with sufficient time for one-on-one interactions among scientists
Previous Zomes Conferences
|I||1999||Israel||The COP9 signalosome, proteasome, and eIF3 at the crossroads of signaling|
|II||2002||Turkey||The COP9 signalosome, proteasome, and eIF3 at the interface between signaling and proteolysis|
|III||2004||Germany||The COP9 signalosome, proteasome, and eIF3 at the interface between signaling and proteolysis|
|IV||2006||USA||The COP9 signalosome, proteasome, and eIF3 at the interface between signaling and proteolysis|
|VI||2010||Israel||Expanding the PCI family beyond proteasome, CSN and eIF3|
|VII||2012||Germany||Ubiquitin-like proteins and their respective PCI complexes|
|VIII||2014||PRC||From system dynamics to biology: Expanding the realm of PCI complexes|
|IX||2017||Italy||PCI complexes and ubiquitin defining a hub for protein homeostasis|
- Deng X-W, Dubiel W, Wei N, Hofmann K, Mundt K, Colicelli J, Kato J, Naumann M, Segal D, Seeger M, Glickman M, Chamovitz DA, Carr A: Unified nomenclature for the COP9 signalosome and its subunits: an essential regulator of development. Trends in Genetics 2000, 16:202–203.
- Chang EC, Schwechheimer C: ZOMES III: the interface between signalling and proteolysis. EMBO Rep 2004, 5:1041–1045.
- Von Arnim AG, Schwechheimer C: Life Is Degrading–Thanks to Some Zomes. Molecular Cell 2006, 23:621–629.
- Pick E, Pintard L: In the land of the rising sun with the COP9 signalosome and related Zomes. Symposium on the COP9 signalosome, Proteasome and eIF3. EMBO Rep 2009, 10:343–348.
- Yu Z, Kleifeld O, Lande-Atir A, Bsoul M, Kleiman M, Krutauz D, Book A, Vierstra RD, Hofmann K, Reis N, Glickman MH, Pick E: Dual function of Rpn5 in two PCI complexes, the 26S proteasome and COP9 signalosome. Mol Biol Cell 2011.
- Luke-Glaser S, Roy M, Larsen B, Le Bihan T, Metalnikov P, Tyers M, Peter M, Pintard L: CIF-1, a Shared Subunit of the COP9/Signalosome and Eukaryotic Initiation Factor 3 Complexes, Regulates MEL-26 Levels in the Caenorhabditis elegans Embryo. Molecular and Cellular Biology 2007, 27:4526–4540.
- Sha Z, Brill LM, Cabrera R, Kleifeld O, Scheliga JS, Glickman MH, Chang EC, Wolf DA: The eIF3 Interactome Reveals the Translasome, a Supercomplex Linking Protein Synthesis and Degradation Machineries. Molecular Cell 2009, 36:141–152.
- Li L, Deng XW: The COP9 signalosome: an alternative lid for the 26S proteasome? Trends in cell biology 2003, 13:507–509.
- Peng Z, Shen Y, Feng S, Wang X, Chitteti BN, Vierstra RD, Deng XW: Evidence for a physical association of the COP9 signalosome, the proteasome, and specific SCF E3 ligases in vivo. Curr Biol 2003, 13:R504–505.
- Guerrero C, Milenković T, Pržulj N, Kaiser P, Huang L: Characterization of the proteasome interaction network using a QTAX-based tag-team strategy and protein interaction network analysis. Proceedings of the National Academy of Sciences 2008, 105:13333.
- Gabriel C. Lander, Eric Estrin, Mary E. Matyskiela, Charlene Bashore, Eva Nogales & Andreas Martin: Complete subunit architecture of the proteasome regulatory particle. Nature 2012, 482:186-191
- Lasker K, Förster F, Bohn S, Walzthoeni T, Villa E, Unverdorben P, Beck F, Aebersold R, Sali A, Baumeister W : Molecular architecture of the 26S proteasome holocomplex determined by an integrative approach. Proceedings of the National Academy of Sciences 2012, 109:1380-1387.
- Lingaraju GM, Bunker RD, Cavadini S, Hess D, Hassiepen U, Renatus M, Fischer ES, Thomä NH. Crystal structure of the human COP9 signalosome. Nature 2014, 512:161-165.
- Scherer PC, Ding Y, Liu Z, Xu J, Mao H, Barrow JC, Wei N, Zheng N, Snyder SH, and Rao F: Inositol hexakisphosphate (IP6) generated by IP5K mediates cullin-COP9 signalosome interactions and CRL function. Proc Natl Acad Sci U S A 2016, 113: 3503-8.
- Mosadeghi R, Reichermeier KM, Winkler M, Schreiber A, Reitsma JM, Zhang Y, Stengel F, Cao J, Kim M, Sweredoski MJ, Hess S, Leitner A, Aebersold R, Peter M, Deshaies RJ, and Enchev RI: Structural and kinetic analysis of the COP9-Signalosome activation and the cullin-RING ubiquitin ligase deneddylation cycle. Elife 2016, 5.
- Cavadini S, Fischer ES, Bunker RD, Potenza A, Lingaraju GM, Goldie KN, Mohamed WI, Faty M, Petzold G, Beckwith RE, Tichkule RB, Hassiepen U, Abdulrahman W, Pantelic RS, Matsumoto S, Sugasawa K, Stahlberg H, and Thoma NH: Cullin-RING ubiquitin E3 ligase regulation by the COP9 signalosome. Nature 2016, 531 : 598-603
- Albert S, Schaffer M, Beck F, Mosalaganti S, Asano S, Thomas HF, Plitzko JM, Beck M, Baumeister W, Engel BD. Proteasomes tether to two distinct sites at the nuclear pore complex.Proc Natl Acad Sci U S A. 2017, 26;114(52):13726-13731
- Kolog Gulko M, Heinrich G, Gross C, Popova B, Valerius O, Neumann P, Ficner R, Braus GH. Sem1 links proteasome stability and specificity to multicellular development.PLoS Genet. 2018 Feb 5;14(2):e1007141.
- Walczak MJ, Petzold G, Thomä NH. Targeted protein degradation: You can glue it too! Nat Chem Biol. 2017 Apr 13;13(5):452-453.