title: Association with cullin partners protects ROC proteins from proteasome-dependent degradation.
abstract: Cullin 1/CDC53 represents a multigene family and has been linked to the ubiquitin-mediated proteolysis of several different proteins. We recently identified two closely related RING finger proteins, ROC1 and ROC2, that share considerable sequence similarity to an APC subunit, APC11, and demonstrated ROC1 as an essential subunit of CUL1 and CDC53 ubiquitin ligases. We report here that the expression of ROC1, ROC2 and APC11 genes are induced by mitogens and remain constant during the cell cycle. Unlike other subunits of SCF and APC E3 ligases, ectopically expressed ROC family proteins are degraded by a proteasome-inhibitor sensitive pathway and are stabilized by associating with cullins. Mutations at the conserved Phe79 and His80 residues in the RING finger of ROC1 diminish its binding with cullins, resulting in a loss of cullin protection and ubiquitin ligase activity. These results suggest a potential mechanism for regulating the activity of ROC-cullin ligases through complex assembly and ROC/APC11 subunit ubiquitination.
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill 27599-7295, USA.
authors.forename: T
authors.initials: T
authors.lastname: Ohta
authors.forename: J J
authors.initials: JJ
authors.lastname: Michel
authors.forename: Y
authors.initials: Y
authors.lastname: Xiong
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D044842:Cullin Proteins; D003546:Cysteine Endopeptidases / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004795:Enzyme Stability; D006868:Hydrolysis; D008025:Ligases / Q000235:genetics / Q000378:metabolism*; D008934:Mitogens / Q000494:pharmacology; D009097:Multienzyme Complexes / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases
chemical_list: D018797:Cell Cycle Proteins; C100318:Cullin 1; D044842:Cullin Proteins; D015853:Cysteine Proteinase Inhibitors; D008934:Mitogens; D009097:Multienzyme Complexes; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D044767:Ubiquitin-Protein Ligases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D008025:Ligases