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 Plk1S (L197F) and Plk1T (L197S/L211A) selectively phosphorylate Ser and Thr, respectively. Plk1S but not Plk1T 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 Thr on Kif2b places these phosphorylation sites under reversible chemical control, as indicated by a sharp increase in the frequency of misaligned chromosomes and prometaphase arrest. Thus, we demonstrate the ability to chemically control a single substrate by a genetic Ser/Thr toggle.
journal_name
Cell Chem Bioljournal_title
Cell chemical biologyauthors
Johnson JM,Hebert AS,Drane QH,Lera RF,Wan J,Weaver BA,Coon JJ,Burkard MEdoi
10.1016/j.chembiol.2020.01.007subject
Has Abstractpub_date
2020-03-19 00:00:00pages
350-362.e8issue
3eissn
2451-9456issn
2451-9448pii
S2451-9456(20)30007-6journal_volume
27pub_type
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