Temporal changes in Hec1 phosphorylation control kinetochore-microtubule attachment stability during mitosis
Keith F DeLuca1, Susanne M A Lens, Jennifer G DeLuca
1Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523, USA.
Journal of Cell Science
|January 27, 2011
Summary
Aurora B kinase phosphorylates Hec1 at kinetochores during mitosis, regulating attachment stability. This phosphorylation is crucial for error correction and is reduced as chromosomes align, ensuring genomic stability.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Accurate chromosome segregation relies on precise kinetochore-microtubule attachment strength.
- Aurora B kinase is known to regulate attachment stability, but its specific kinetochore targets are not fully understood.
Purpose of the Study:
- To identify and characterize the phosphorylation targets of Aurora B kinase at the kinetochore.
- To elucidate the role of Hec1 phosphorylation in regulating kinetochore-microtubule attachments during mitosis.
Main Methods:
- Phosphoproteomic analysis to identify phosphorylated serine residues on Hec1.
- Mitotic progression studies in human cells.
- Immunofluorescence microscopy to assess protein localization and phosphorylation status.
Main Results:
- Multiple serine residues in the N-terminus of Hec1 are phosphorylated by Aurora B kinase during mitosis.
- Hec1 phosphorylation is high in early mitosis and decreases upon chromosome bi-orientation.
- Dephosphorylated Hec1 is resistant to rephosphorylation upon loss of attachment or tension.
- Aurora B kinase persists at the outer kinetochore even after Hec1 dephosphorylation.
Conclusions:
- Hec1 phosphorylation by Aurora B kinase destabilizes kinetochore-microtubule attachments, facilitating error correction in early mitosis.
- Hec1 dephosphorylation is essential for maintaining stable kinetochore-microtubule attachments in late mitosis.
- Regulation of Hec1 phosphorylation may involve mechanisms beyond simple kinase localization.
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