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Role of Hec1 in Spindle Checkpoint Signaling and Kinetochore Recruitment of Mad1/Mad2
Abstract
The spindle checkpoint delays sister chromatid separation until all chromosomes have undergone bipolar spindle attachment. Checkpoint failure may result in chromosome mis-segregation and may contribute to tumorigenesis. We showed that the human protein Hec1 was required for the recruitment of Mps1 kinase and Mad1/Mad2 complexes to kinetochores. Depletion of Hec1 impaired chromosome congression and caused persistent activation of the spindle checkpoint, indicating that high steady-state levels of Mad1/Mad2 complexes at kinetochores were not essential for checkpoint signaling. Simultaneous depletion of Hec1 and Mad2 caused catastrophic mitotic exit, making Hec1 an attractive target for the selective elimination of spindle checkpoint–deficient cells.
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Cites
Genetic instabilities in human cancers
Lengauer, C., Kinzler, K. W., & Vogelstein, B. (1998) · Nature · doi:10.1038/25292 · Cited by 4,168
Cited by
The spindle-assembly checkpoint in space and time
Musacchio, A., & Salmon, E. D. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2163 · Cited by 2,227
Glinsky, G. V., Berezovska, O., & Glinskii, A. B. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23412 · Cited by 916
The molecular biology of spindle assembly checkpoint signaling dynamics.
Musacchio, A. (2015) · Current Biology · doi:10.1016/j.cub.2015.08.051 · Cited by 778
The spindle checkpoint: structural insights into dynamic signalling
Musacchio, A., & Hardwick, K. G. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm929 · Cited by 531
Timing and Checkpoints in the Regulation of Mitotic Progression
Meraldi, P., Draviam, V. M., & Sorger, P. K. (2004) · Developmental Cell · doi:10.1016/j.devcel.2004.06.006 · Cited by 469
Metadata
- Authors
- Martin-Lluesma, S., Stucke, V. M., & Nigg, E. A.
- Venue
- Science
- Published
- 2002-09-27
- Volume
- 297
- Issue
- 5590
- Pages
- 2267-2270
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2089844705
- Cited by
- 427
- References
- 1
- FWCI
- 12.22
- Type
- journal article
- Language
- en
- Open access
- closed
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