title: CAND1 binds to unneddylated CUL1 and regulates the formation of SCF ubiquitin E3 ligase complex.
abstract: The SCF ubiquitin E3 ligase regulates ubiquitin-dependent proteolysis of many regulatory proteins such as p27(Kip1), IkappaB, and beta-catenin. We report the isolation of a CUL1 binding protein, p120(CAND1). We found the majority of CUL1 is in a complex with CAND1 and ROC1 independent of SKP1 and F box protein SKP2. Both in vivo and in vitro, CAND1 prevents the binding of SKP1 and SKP2 to CUL1 while dissociation of CAND1 from CUL1 promotes the reverse reaction. Neddylation of CUL1 or the presence of SKP1 and ATP causes CAND1 dissociation. Our data suggest that CAND1 regulates the formation of the SCF complex, and its dissociation from CUL1 is coupled with the incorporation of F box proteins into the SCF complex, causing their destabilization.
authors.affiliation: Department of Genetics, Yale University School of Medicine, 333 Cedar Street, Yale University, New Haven, CT 06520, USA.
authors.forename: Jianyu
authors.initials: J
authors.lastname: Zheng
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Yang
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Harrell
authors.forename: Sophia
authors.initials: S
authors.lastname: Ryzhikov
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Shim
authors.forename: Karin
authors.initials: K
authors.lastname: Lykke-Andersen
authors.forename: Ning
authors.initials: N
authors.lastname: Wei
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.forename: Ryuji
authors.initials: R
authors.lastname: Kobayashi
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D010453:Peptide Synthases / Q000378:metabolism*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D044843:SKP Cullin F-Box Protein Ligases; D014157:Transcription Factors; D025801:Ubiquitin / Q000378:metabolism
chemical_list: C486317:CAND1 protein, human; D002352:Carrier Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D014157:Transcription Factors; D025801:Ubiquitin; D000255:Adenosine Triphosphate; D044843:SKP Cullin F-Box Protein Ligases; D010453:Peptide Synthases