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J Biol Chem. 2013 Dec 13;288(50):36149-59. doi: 10.1074/jbc.M113.507970. Epub 2013 Nov 1.

Phosphorylation of microtubule-binding protein Hec1 by mitotic kinase Aurora B specifies spindle checkpoint kinase Mps1 signaling at the kinetochore.

Author information

1
From the Anhui Key Laboratory of Cellular Dynamics and Chemical Biology, University of Science and Technology of China, Hefei 230026, China.

Abstract

The spindle assembly checkpoint (SAC) is a quality control device to ensure accurate chromosome attachment to spindle microtubule for equal segregation of sister chromatid. Aurora B is essential for SAC function by sensing chromosome bi-orientation via spatial regulation of kinetochore substrates. However, it has remained elusive as to how Aurora B couples kinetochore-microtubule attachment to SAC signaling. Here, we show that Hec1 interacts with Mps1 and specifies its kinetochore localization via its calponin homology (CH) domain and N-terminal 80 amino acids. Interestingly, phosphorylation of the Hec1 by Aurora B weakens its interaction with microtubules but promotes Hec1 binding to Mps1. Significantly, the temporal regulation of Hec1 phosphorylation orchestrates kinetochore-microtubule attachment and Mps1 loading to the kinetochore. Persistent expression of phosphomimetic Hec1 mutant induces a hyperactivation of SAC, suggesting that phosphorylation-elicited Hec1 conformational change is used as a switch to orchestrate SAC activation to concurrent destabilization of aberrant kinetochore attachment. Taken together, these results define a novel role for Aurora B-Hec1-Mps1 signaling axis in governing accurate chromosome segregation in mitosis.

KEYWORDS:

Cenp-e; Checkpoint; Checkpoint Control; Kinetochore; Mitosis; Mitotic Spindle; Phosphorylation

PMID:
24187132
PMCID:
PMC3861662
DOI:
10.1074/jbc.M113.507970
[Indexed for MEDLINE]
Free PMC Article
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