Sequential multisite phospho-regulation of KNL1-BUB3 interfaces at mitotic kinetochores - PubMed (original) (raw)
. 2015 Mar 5;57(5):824-835.
doi: 10.1016/j.molcel.2014.12.036. Epub 2015 Feb 5.
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- PMID: 25661489
- DOI: 10.1016/j.molcel.2014.12.036
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Sequential multisite phospho-regulation of KNL1-BUB3 interfaces at mitotic kinetochores
Mathijs Vleugel et al. Mol Cell. 2015.
Free article
Abstract
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.
Copyright © 2015 Elsevier Inc. All rights reserved.
Comment in
- The (phospho) needle in the (MELT) Haystack.
Faesen AC, Musacchio A. Faesen AC, et al. Mol Cell. 2015 Mar 5;57(5):765-766. doi: 10.1016/j.molcel.2015.02.026. Mol Cell. 2015. PMID: 25747656
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