title: CUL7: A DOC domain-containing cullin selectively binds Skp1.Fbx29 to form an SCF-like complex.
abstract: Selective protein degradation targeted by members of the F-box protein family plays pivotal roles in cell biology. It is widely accepted that an F-box protein directs substrate ubiquitination within a Skp1.CUL1.F-box protein.ROC1 (SCF-ROC1) E3 ubiquitin ligase complex. This assembly utilizes the CUL1 molecular scaffold, allowing the F-box protein to position its bound substrate for ubiquitination by a ROC1-recruited E2-conjugating enzyme. Here, we describe an alternative mechanism for assembling an F-box protein-based E3 complex through a previously uncharacterized cullin, CUL7, identified by mass spectrometry as a ROC1-interacting protein. CUL7 is a large polypeptide containing a cullin domain, which is responsible for ROC1 binding, and a DOC domain, which is also present in the anaphase-promoting complex. Remarkably, CUL7 assembles an SCF-ROC1-like E3 ubiquitin ligase complex consisting of Skp1, CUL7, the Fbx29 F-box protein, and ROC1. In contrast to CUL1 that binds Skp1 by itself, CUL7 interacts with the Skp1.Fbx29 complex, but not with Skp1 alone. Strikingly, CUL7 selectively interacts with Skp1.Fbx29 but not with Skp1.betaTRCP2 or Skp1.Skp2. Thus, CUL7 may define a previously uncharacterized, Fbx29-mediated, and ubiquitin-dependent proteolysis pathway.
authors.affiliation: Derald H. Ruttenberg Cancer Center and Department of Human Genetics, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029-6574, USA.
authors.forename: Dora C
authors.initials: DC
authors.lastname: Dias
authors.forename: Georgia
authors.initials: G
authors.lastname: Dolios
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.forename: Zhen-Qiang
authors.initials: ZQ
authors.lastname: Pan
mesh_terms: D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000378:metabolism*; D044842:Cullin Proteins; D006801:Humans; D008025:Ligases / Q000378:metabolism; D010453:Peptide Synthases / Q000378:metabolism*; D044786:S-Phase Kinase-Associated Proteins; D044843:SKP Cullin F-Box Protein Ligases; D044767:Ubiquitin-Protein Ligases
chemical_list: D018797:Cell Cycle Proteins; C100318:Cullin 1; D044842:Cullin Proteins; D044786:S-Phase Kinase-Associated Proteins; D044843:SKP Cullin F-Box Protein Ligases; D044767:Ubiquitin-Protein Ligases; D008025:Ligases; D010453:Peptide Synthases