Regulation of cullin-RING E3 ubiquitin-ligases by neddylation and dimerization

Merlet, J.; Burger, J.; Gomes, J.-E.; Pintard, L.
June 2009
Cellular & Molecular Life Sciences;Jun2009, Vol. 66 Issue 11/12, p1924
Academic Journal
Cullin-RING E3 ubiquitin-Ligases (CRLs) are the most prominent class of ubiquitin-ligases. By controlling the stability of a cohort of key regulators, CRLs impinge on many cellular and biological processes such as immunity, development, transcription, cell signalling and cell cycle progression. CRLs are multi-subunit complexes composed of a catalytic site and a substrate recognition module nucleated around a cullin scaffold protein. Most eukaryotic genomes encode at least five distinct cullins, and each of these cullins recruits a specific substrate-recognition module such that CRL complexes are modular. Despite their considerable diversity, CRLs are regulated by similar mechanisms. In particular, recent observations indicate that conformational variability induced by CRL dimerization and by conjugation of the ubiquitin-like protein NEDD8 on the cullin subunit stimulates substrate polyubiquitination. In this review, we discuss the composition of CRL complexes and the various molecular mechanisms controlling their activity.


Related Articles

  • Two E3 ubiquitin ligases, SCF-Skp2 and DDB1-Cul4, target human Cdt1 for proteolysis. Nishitani, Hideo; Sugimoto, Nozomi; Roukos, Vassilis; Nakanishi, Yohsuke; Saijo, Masafumi; Obuse, Chikashi; Tsurimoto, Toshiki; Nakayama, Keiichi I; Nakayama, Keiko; Fujita, Masatoshi; Lygerou, Zoi; Nishimoto, Takeharu // EMBO Journal;3/8/2006, Vol. 25 Issue 5, p1126 

    Replication licensing is carefully regulated to restrict replication to once in a cell cycle. In higher eukaryotes, regulation of the licensing factor Cdt1 by proteolysis and Geminin is essential to prevent re-replication. We show here that the N-terminal 100 amino acids of human Cdt1 are...

  • "Cullin 4 makes its mark on chromatin.". Qian Dai; Hengbin Wang // Cell Division;2006, Vol. 1, p14 

    Cullin 4 (Cul4), a member of the evolutionally conserved cullin protein family, serves as a scaffold to assemble multisubunit ubiquitin E3 ligase complexes. Cul4 interacts with the Ring fingercontaining protein ROC1 through its C-terminal cullin domain and with substrate recruiting subunit(s)...

  • Exploitation of Eukaryotic Ubiquitin Signaling Pathways by Effectors Translocated by Bacterial Type III and Type IV Secretion Systems. Angot, Aurélie; Vergunst, Annette; Genin, Stéphane; Peeters, Nemo // PLoS Pathogens;Jan2007, Vol. 3 Issue 1, p1 

    The specific and covalent addition of ubiquitin to proteins, known as ubiquitination, is a eukaryotic-specific modification central to many cellular processes, such as cell cycle progression, transcriptional regulation, and hormone signaling. Polyubiquitination is a signal for the 26S proteasome...

  • The BTB protein MEL-26 is a substrate-specific adaptor of the CUL-3 ubiquitin-ligase. Pintard,, Lionel; Willis, John H.; Willems, Andrew; Johnson, Jacque-Lynne F.; Sryko, Martin; Kurz, Thimo; Glaser, Sarah; Mains, Paul E.; Tyers, Mike; Bowerman, Bruce; Peter, Matthias // Nature;9/18/2003, Vol. 425 Issue 6955, p311 

    Many biological processes, such as development and cell cycle progression are tightly controlled by selective ubiquitin-dependent degradation of key substrates. In this pathway, the E3-ligase recognizes the substrate and targets it for degradation by the 26S proteasome. The SCF (Skp1-Cul1-F-box)...

  • Evidence for dysregulation of cell cycle by human polymavirus, JCV, late auxiliary protein. Darbinyan, Armine; Darbinian, Nune; Safak, Mahmut; Radhakrishnan, Sujatha; Giordano, Antonio; Khalili, Kamel // Oncogene;8/15/2002, Vol. 21 Issue 36, p5574 

    Presents a study that demonstrated the evidence for dysregulation of cell cycle by human polyomavirus, JCV, and late auxiliary protein. Composition of the JCV genome; Analysis of Agnoprotein producing cells which exhibited a different pattern of the cell cycle than the control cells; Approaches...

  • SCFCyclin F controls centrosome homeostasis and mitotic fidelity through CP110 degradation. D'Angiolella, Vincenzo; Donato, Valerio; Vijayakumar, Sangeetha; Saraf, Anita; Florens, Laurence; Washburn, Michael P.; Dynlacht, Brian; Pagano, Michele // Nature;7/1/2010, Vol. 466 Issue 7302, p138 

    Generally, F-box proteins are the substrate recognition subunits of SCF (Skp1–Cul1–F-box protein) ubiquitin ligase complexes, which mediate the timely proteolysis of important eukaryotic regulatory proteins. Mammalian genomes encode roughly 70 F-box proteins, but only a handful...

  • APC/C regulation of axonal growth and synaptic functions in postmitotic neurons: the Liprin- $${\varvec \alpha}$$ connection. Teng, F. Y. H.; Tang, B. L. // Cellular & Molecular Life Sciences;Jul2005, Vol. 62 Issue 14, p1571 

    Protein ubiquitination has critical roles in neuronal physiology and defects in protein ubiquitination have been implicated in neurodegenerative pathology. The anaphase-promoting complex/cyclosome (APC/C) is one of two key E3 ubiquitin ligase complexes that functions in regulating cell cycle...

  • RATCHETS AND CLOCKS: THE CELL CYCLE, UBIQUITYLATION AND PROTEIN TURNOVER. Reed, Steven I. // Nature Reviews Molecular Cell Biology;Nov2003, Vol. 4 Issue 11, p855 

    Describes the models of the cell cycle and the roles of regulated proteolysis. Reasons behind the prominent role of proteolysis in cell cycle control; Information on the key cell cycle regulatory proteins targeted by ubiquitin-mediated proteolysis; Strategies for ubiquitylation.

  • How APC/C orders destruction. Buschhorn, Bettina A.; Peters, Jan-Michael // Nature Cell Biology;Mar2006, Vol. 8 Issue 3, p209 

    The anaphase-promoting complex/cyclosome (APC/C) is a ubiquitin ligase that controls cell-cycle progression by targeting proteins for destruction by the 26S proteasome. The APC/C is active throughout late mitosis and G1 phase but APC/C substrates are degraded in a specific order. A recent study...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics