title: Skp1 Independent Function of Cdc53/Cul1 in F-box Protein Homeostasis.
abstract: Abundance of substrate receptor subunits of Cullin-RING ubiquitin ligases (CRLs) is tightly controlled to maintain the full repertoire of CRLs. Unbalanced levels can lead to sequestration of CRL core components by a few overabundant substrate receptors. Numerous diseases, including cancer, have been associated with misregulation of substrate receptor components, particularly for the largest class of CRLs, the SCF ligases. One relevant mechanism that controls abundance of their substrate receptors, the F-box proteins, is autocatalytic ubiquitylation by intact SCF complex followed by proteasome-mediated degradation. Here we describe an additional pathway for regulation of F-box proteins on the example of yeast Met30. This ubiquitylation and degradation pathway acts on Met30 that is dissociated from Skp1. Unexpectedly, this pathway required the cullin component Cdc53/Cul1 but was independent of the other central SCF component Skp1. We demonstrated that this non-canonical degradation pathway is critical for chromosome stability and effective defense against heavy metal stress. More importantly, our results assign important biological functions to a sub-complex of cullin-RING ligases that comprises Cdc53/Rbx1/Cdc34, but is independent of Skp1.
authors.affiliation: Department of Biological Chemistry, College of Medicine, University of California Irvine, Irvine, California, United States of America.
authors.forename: Radhika
authors.initials: R
authors.lastname: Mathur
authors.affiliation: Department of Biological Chemistry, College of Medicine, University of California Irvine, Irvine, California, United States of America.
authors.forename: James L
authors.initials: JL
authors.lastname: Yen
authors.affiliation: Department of Biological Chemistry, College of Medicine, University of California Irvine, Irvine, California, United States of America.
authors.forename: Peter
authors.initials: P
authors.lastname: Kaiser
mesh_terms: D000595:Amino Acid Sequence; D002104:Cadmium / Q000633:toxicity; D002453:Cell Cycle / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D044842:Cullin Proteins / Q000235:genetics*; D044783:F-Box Proteins / Q000235:genetics*; D006706:Homeostasis / Q000187:drug effects; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D059748:Proteolysis / Q000187:drug effects; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics*; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D043743:Ubiquitin-Protein Ligase Complexes / Q000235:genetics*; D054875:Ubiquitination / Q000235:genetics*; D014452:Ubiquitins / Q000235:genetics
chemical_list: C100988:Cdc53 protein, S cerevisiae; D044842:Cullin Proteins; D044783:F-Box Proteins; C470285:MET30 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014452:Ubiquitins; D002104:Cadmium; D043743:Ubiquitin-Protein Ligase Complexes; D044843:SKP Cullin F-Box Protein Ligases; C120507:SKP1 protein, S cerevisiae