The Prozone Effect Accounts for the Paradoxical Function of the Cdk-Binding Protein Suc1/Cks

Autor: Sang Hoon Ha, Sun Young Kim, James E. Ferrell Jr.
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: Cell Reports, Vol 14, Iss 6, Pp 1408-1421 (2016)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2016.01.033
Popis: 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.
Databáze: Directory of Open Access Journals