A Genetic Toggle for Chemical Control of Individual Plk1 Substrates.

ABSTRACT: Polo-like kinase 1 has hundreds of substrates and multiple functions that operate within the ∼60 min of mitosis. Herein, we describe a chemical-genetic system that allows particular substrates to be "toggled" into or out of chemical control using engineered phosphoacceptor selectivity. Biochemical assays and phosphoproteomic analysis of mitotic cell extracts showed that Plk1^S (L197F) and Plk1^T (L197S/L211A) selectively phosphorylate Ser and Thr, respectively. Plk1^S but not Plk1^T sustains mitotic progression to anaphase, affording the opportunity to toggle substrate residues between Ser and Thr to place them under chemical control. Using this system, we evaluated Kif2b, a known substrate of Plk1 that regulates chromosome alignment. Toggling Ser to

SUBMITTER: Johnson JM 

PROVIDER: S-EPMC7239509 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature