title: The Prozone Effect Accounts for the Paradoxical Function of the Cdk-Binding Protein Suc1/Cks.
abstract: Previous work has shown that Suc1/Cks proteins can promote the hyperphosphorylation of primed Cdk1 substrates through the formation of ternary Cdk1-Cks-phosphosubstrate complexes. This raises the possibility that Cks proteins might be able to both facilitate and interfere with hyperphosphorylation through a mechanism analogous to the prozone effect in antigen-antibody interactions, with substoichiometric Cks promoting the formation of Cdk1-Cks-phosphosubstrate complexes and suprastoichiometric Cks instead promoting the formation of Cdk1-Cks and Cks-phosphosubstrate complexes. We tested this hypothesis through a combination of theory, proof-of-principle experiments with oligonucleotide annealing, and experiments on the interaction of Xenopus cyclin B1-Cdk1-Cks2 with Wee1A in vitro and in Xenopus extracts. Our findings help explain why both Cks under-expression and overexpression interfere with cell-cycle progression and provide insight into the regulation of the Cdk1 system.
authors: Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305-5174, USA.
authors: Sang Hoon
authors: SH
authors: Ha
authors: Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305-5174, USA.
authors: Sun Young
authors: SY
authors: Kim
authors: Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305-5174, USA; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305-5174, USA. Electronic address: james.ferrell@stanford.edu.
authors: James E
authors: JE
authors: Ferrell
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D016367:Baculoviridae / Q000235:genetics / Q000378:metabolism; D016203:CDC2 Protein Kinase / Q000235:genetics* / Q000378:metabolism; D042846:CDC2-CDC28 Kinases / Q000235:genetics* / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D056744:Cyclin B1 / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D000072417:Protein Domains; D017433:Protein Structure, Secondary; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D061987:Sf9 Cells; D015398:Signal Transduction; D018411:Spodoptera; D029867:Xenopus Proteins / Q000235:genetics* / Q000378:metabolism; D014982:Xenopus laevis / Q000235:genetics*; D015053:Zygote / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D056744:Cyclin B1; C440489:FRS2 protein, Xenopus; D009687:Nuclear Proteins; D009841:Oligonucleotides; D010750:Phosphoproteins; D011994:Recombinant Proteins; D029867:Xenopus Proteins; C530005:WEE1 protein, Xenopus; D011505:Protein-Tyrosine Kinases; D016203:CDC2 Protein Kinase; D042846:CDC2-CDC28 Kinases