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Jun (2007); 0:
SCF E3 -mediated autoubiquitination negatively regulates activity of the Cdc34 E2 but plays a nonessential role in the catalytic cycle in vitro and in vivo-
Scaglione KM, Bansal P, Deffenbaugh AE, Kiss A, Moore JM, Korolev S, Cocklin R, Goebl M, Kitagawa K, Skowyra D
Edward A- Doisy Dept- of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St- Louis, MO 63104; Department of Molecular Pharmacology, St- Jude Children's Research Hospital, Memphis, TN 38105-2794; Department of Biochemistry and Molecular Biology and the Walther Oncology Center, Indiana University School of Medicine, Indianapolis, IN 46202-
Abstract: One of the several yet unexplained aspects of the mechanism by which the Cdc34-SCF RING-type ubiquitin ligases work is the marked stimulation of Cdc34 autoubiquitination, a phenomenon of unknown mechanism and significance- In in vitro experiments with single lysine-containing Cdc34 mutant proteins of S- cerevisiae we find that the SCF-mediated stimulation of autoubiquitination is limited to specific N-terminal lysines modified via an inter-molecular mechanism- In a striking contrast, SCF quenches autoubiquitination of C-terminal lysines catalyzed in an intra-molecular manner- Unlike autoubiquitination of the C-terminal lysines, which has no functional consequence, autoubiquitination of the N-terminal lysines inhibits Cdc34- This autoinhibitory mechanism plays a nonessential role in the catalytic cycle, as the lysine-less -K0-Cdc34-DeltaC- is undistinguishable from Cdc34-DeltaC- in ubiquitination of the prototype SCF-Cdc4- substrate Sic1 in vitro and replacement of CDC34 gene with either -K0-cdc34-DeltaC- or cdc34-DeltaC- allele in yeast has no cell cycle phenotype- We discuss implications of these findings on the mechanism of Cdc34 function with SCF-
[PUBMED: 17562869] Download Biogrid Interactions in a variety of formats including PSI FormatPUBMED
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Chris Stark, Bobby-Joe Breitkreutz, Teresa Reguly, Lorrie Boucher, Ashton Breitkreutz, Mike Tyers.
Nucleic Acids Res. Jan 1;34:D535-9.