Sequential multisite phospho-regulation of KNL1-BUB3 interfaces at mitotic kinetochores
| Autor: | Mathijs Vleugel, Susanne M.A. Lens, Vincent Groenewold, Manja Omerzu, Geert J. P. L. Kops, Michael A. Hadders |
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| Rok vydání: | 2014 |
| Předmět: |
Models
Molecular Amino Acid Motifs Sequence Homology Cell Cycle Proteins Plasma protein binding Repetitive Sequences chemistry.chemical_compound 0302 clinical medicine Models Phosphorylation Kinetochores Poly-ADP-Ribose Binding Proteins 0303 health sciences Kinetochore Nocodazole Protein-Tyrosine Kinases Protein-Serine-Threonine Kinases Tubulin Modulators 3. Good health Cell biology Amino Acid Spindle checkpoint RNA Interference Microtubule-Associated Proteins Protein Binding Repetitive Sequences Amino Acid Protein Structure Microtubule-associated protein BUB3 Immunoblotting Molecular Sequence Data BUB1 Mitosis Biology Protein Serine-Threonine Kinases Time-Lapse Imaging 03 medical and health sciences Humans Amino Acid Sequence Molecular Biology 030304 developmental biology Sequence Homology Amino Acid fungi Molecular Cell Biology Molecular biology Protein Structure Tertiary chemistry Mutation M Phase Cell Cycle Checkpoints Tertiary 030217 neurology & neurosurgery HeLa Cells |
| Zdroj: | Molecular Cell, 57(5), 824. Cell Press |
| ISSN: | 1097-4164 1097-2765 |
| Popis: | Regulated recruitment of the kinase-adaptor complex BUB1/BUB3 to kinetochores is crucial for correcting faulty chromosome-spindle attachments and for spindle assembly checkpoint (SAC) signaling. BUB1/BUB3 localizes to kinetochores by binding phosphorylated MELT motifs (MELpT) in the kinetochore scaffold KNL1. Human KNL1 has 19 repeats that contain a MELT-like sequence. The repeats are, however, larger than MELT, and repeat sequences can vary significantly. Using systematic screening, we show that only a limited number of repeats is "active." Repeat activity correlates with the presence of a vertebrate-specific SHT motif C-terminal to the MELT sequence. SHT motifs are phosphorylated by MPS1 in a manner that requires prior phosphorylation of MELT. Phospho-SHT (SHpT) synergizes with MELpT in BUB3/BUB1 binding in vitro and in cells, and human BUB3 mutated in a predicted SHpT-binding surface cannot localize to kinetochores. Our data show sequential multisite regulation of the KNL1-BUB1/BUB3 interaction and provide mechanistic insight into evolution of the KNL1-BUB3 interface. |
| Databáze: | OpenAIRE |
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