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Inhibitor‐3 ensures bipolar mitotic spindle attachment by limiting association of SDS 22 with kinetochore‐bound protein phosphatase‐1
Author(s) -
Eiteneuer Annika,
Seiler Jonas,
Weith Matthias,
Beullens Monique,
Lesage Bart,
Krenn Veronica,
Musacchio Andrea,
Bollen Mathieu,
Meyer Hemmo
Publication year - 2014
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201489054
Subject(s) - kinetochore , biology , anaphase , mitosis , microbiology and biotechnology , aurora b kinase , phosphatase , spindle checkpoint , spindle apparatus , microtubule , metaphase , chromosome segregation , phosphorylation , cell division , biochemistry , chromosome , cell cycle , cell , gene
Faithful chromosome segregation during mitosis is tightly regulated by opposing activities of Aurora B kinase and protein phosphatase‐1 ( PP 1). PP 1 function at kinetochores has been linked to SDS 22, but the exact localization of SDS 22 and how it affects PP 1 are controversial. Here, we confirm that SDS 22 is required for PP 1 activity, but show that SDS 22 does not normally localize to kinetochores. Instead, SDS 22 is kept in solution by formation of a ternary complex with PP 1 and inhibitor‐3 (I3). Depletion of I3 does not affect the amount of PP 1 at kinetochores but causes quantitative association of SDS 22 with PP 1 on KNL 1 at the kinetochore. Such accumulation of SDS 22 at kinetochores interferes with PP 1 activity and inhibits Aurora B threonine‐232 dephosphorylation, which leads to increased Aurora B activity in metaphase and persistence in anaphase accompanied with segregation defects. We propose a model in which I3 regulates an SDS 22‐mediated PP 1 activation step in solution that precedes SDS 22 dissociation and transfer of PP 1 to kinetochores, and which is required for PP 1 to efficiently antagonize Aurora B.