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dc.contributor.authorBosu, Dimple Rani
dc.date.accessioned2014-03-04T16:20:25Z
dc.date.available2014-03-04T16:20:25Z
dc.date.issued2008-12
dc.identifier.otherbosu_dimple_r_200812_phd
dc.identifier.urihttp://purl.galileo.usg.edu/uga_etd/bosu_dimple_r_200812_phd
dc.identifier.urihttp://hdl.handle.net/10724/25133
dc.description.abstractCullins function in multisubunit ubiquitin ligase (E3) complexes to promote the ubiquitin-mediated proteolysis of substrates and regulate a wide range of cellular processes. CAND1 is a HEAT repeat protein that binds to cullins and regulates their ubiquitin ligase activity by inhibiting the formation of full E3 complexes. All cullins are modified by the covalent linkage of Nedd8, which is a ubiquitin-like protein that is required for full cullin activity. CAND1 cannot bind a cullin that is neddylated but it forms tight complexes with the unneddylated form of cullins. It was originally believed that neddylation of CUL1 bound to CAND1 could dissociate CAND1 and trigger active SCF complex formation (Jidong Liu, Molecular Cell, December 2002). However, more recent biochemical analysis and the crystal structure of CAND1 bound to CUL1 revealed that neddylation can not decouple CAND1 from CUL1 (Goldenberg, Cell, November 2004). Currently, it is not known how CAND1 that is bound to a cullin can be dissociated, or the physiological significance of CAND1 binding to cullin proteins in vivo. In this study we determined the roles of CAND-1 in modulating the functions of the C. elegans cullins. C. elegans has only a single CAND1 ortholog: cand-1( Y102A5A.1). We have identified CAND-1 as a major component of CUL-2 and CUL-4 complexes. Analysis with the yeast two-hybrid system indicates that both the N- and C-terminal domains of CAND-1 interact with all six C. elegans cullin proteins. The mutant phenotype of cand-1 does not show any major cullin loss of function phenotypes. We have determined the neddylation level of CUL-2 and CUL-4 in cand-1 mutant and found that the level of neddylation increased substantially for both cullins, indicating that CAND-1 negatively regulates neddylation in vivo. We also carried out a genomic screen for cand-1 enhancers, and found 18 enhancers that are potential regulator(s) of CAND-1 and the CRLs (Cullin Ring ubiquitin Ligase) activation cycle.
dc.languageeng
dc.publisheruga
dc.rightspublic
dc.subjectCaenorhabditis elegans
dc.subjectCAND1
dc.subjectCUL-1
dc.subjectCUL-2
dc.subjectCUL-4
dc.subjectSkp1
dc.subjectF-box protein
dc.subjectRbx1
dc.subjectNedd8
dc.subjectcand-1
dc.subjectY102A5A.1
dc.subjectcell cycle
dc.subjectcullin
dc.subjectubiquitin
dc.subjectubiquitin ligase and CRL..
dc.titleCAND-1 and regulation of cullin RING ubiquitin ligases in C. elegans
dc.typeDissertation
dc.description.degreePhD
dc.description.departmentCellular Biology
dc.description.majorCellular Biology
dc.description.advisorEdward Kipreos
dc.description.committeeEdward Kipreos
dc.description.committeeJacek Gaertig
dc.description.committeeMarcus Fechheimer
dc.description.committeeScott Dougan
dc.description.committeeHaini Cai


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