Lu, G. et al. The myeloma drug lenalidomide promotes the cereblon-dependent destruction of Ikaros proteins. Science 343, 305–309 (2014) Enchev, R. I. et al. Structural basis for a reciprocal regulation between SCF and CSN. Cell Rep . 2, 616–627 (2012) Angers, S. et al. Molecular architecture and assembly of the DDB1–CUL4A ubiquitin ligase machinery. Nature 443, 590–593 (2006)

Center for Cellular Imaging and NanoAnalytics, Biozentrum, University of Basel, Basel, 4058, Switzerland Lyapina, S. et al. Promotion of NEDD–CUL1 conjugate cleavage by COP9 signalosome. Science 292, 1382–1385 (2001) There are locations throughout the country that are home to this program which specializes in repair and service on Ford vehicles. Groisman, R. et al. The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage. Cell 113, 357–367 (2003)Kia has a national training center where mechanics are sent to attain all of the skills and knowledge needed to become an expert in Kia vehicles. Emberley, E. D., Mosadeghi, R. & Deshaies, R. J. Deconjugation of Nedd8 from Cul1 is directly regulated by Skp1-F-box and substrate, and the COP9 signalosome inhibits deneddylated SCF by a noncatalytic mechanism. J. Biol. Chem. 287, 29679–29689 (2012) Fischer, E. S. et al. The molecular basis of CRL4 DDB2/CSA ubiquitin ligase architecture, targeting, and activation. Cell 147, 1024–1039 (2011)

Fischer, E. S. et al. Structure of the DDB1–CRBN E3 ubiquitin ligase in complex with thalidomide. Nature 512, 49–53 (2014) Sugasawa, K. et al. UV-induced ubiquitylation of XPC protein mediated by UV-DDB-ubiquitin ligase complex. Cell 121, 387–400 (2005) Brownell, J. E. et al. Substrate-assisted inhibition of ubiquitin-like protein-activating enzymes: the NEDD8 E1 inhibitor MLN4924 forms a NEDD8–AMP mimetic in situ. Mol. Cell 37, 102–111 (2010)Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, 02215, Massachusetts, USA Scrima, A. et al. Structural basis of UV DNA-damage recognition by the DDB1–DDB2 complex. Cell 135, 1213–1223 (2008) Novartis Institutes for Biomedical Research, 250 Massachusetts Avenue, Cambridge, 02139, Massachusetts, USA