The N-terminus of rodent and human MAD1 confers species-specific stringency to spindle assembly checkpoint

K. Haller; K. V. Kibler; T. Kasai; Y. H. Chi; J. M. Peloponese; V. S.R.K. Yedavalli; K. T. Jeang

doi:10.1038/sj.onc.1209259

The N-terminus of rodent and human MAD1 confers species-specific stringency to spindle assembly checkpoint

K. Haller, K. V. Kibler, T. Kasai, Y. H. Chi, J. M. Peloponese, V. S.R.K. Yedavalli, K. T. Jeang

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

Abstract

The spindle assembly checkpoint (SAC) guards against chromosomal mis-segregation and the emergence of aneuploidy. SAC in higher eukaryotes includes at least 10 proteins including MAD1-3, BUB1-3, and Msp1. A long-standing observation has been that rodent cells are more tolerant of microtubule toxins than primate cells indicating that SAC function is more relaxed in the former than the latter. Here, we report on an unexpected functional difference between the rodent and human MAD1 component of the respective SAC. Ectopic expression of human MAD1 in mouse and hamster cells corrected a relaxed SAC to a more stringent form. Our findings posit MAD1 as a species-specific determinant which influences the stringency of cellular response to microtubule depolymerization and spindle damage.

Original language	English (US)
Pages (from-to)	2137-2147
Number of pages	11
Journal	Oncogene
Volume	25
Issue number	15
DOIs	https://doi.org/10.1038/sj.onc.1209259
State	Published - Apr 6 2006

Keywords

Aneuploidy
Cellular transformation
Chromosomal instability
Mitotic arrest
Spindle assembly checkpoint

ASJC Scopus subject areas

Molecular Biology
Genetics
Cancer Research

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10.1038/sj.onc.1209259

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title = "The N-terminus of rodent and human MAD1 confers species-specific stringency to spindle assembly checkpoint",

abstract = "The spindle assembly checkpoint (SAC) guards against chromosomal mis-segregation and the emergence of aneuploidy. SAC in higher eukaryotes includes at least 10 proteins including MAD1-3, BUB1-3, and Msp1. A long-standing observation has been that rodent cells are more tolerant of microtubule toxins than primate cells indicating that SAC function is more relaxed in the former than the latter. Here, we report on an unexpected functional difference between the rodent and human MAD1 component of the respective SAC. Ectopic expression of human MAD1 in mouse and hamster cells corrected a relaxed SAC to a more stringent form. Our findings posit MAD1 as a species-specific determinant which influences the stringency of cellular response to microtubule depolymerization and spindle damage.",

keywords = "Aneuploidy, Cellular transformation, Chromosomal instability, Mitotic arrest, Spindle assembly checkpoint",

author = "K. Haller and Kibler, {K. V.} and T. Kasai and Chi, {Y. H.} and Peloponese, {J. M.} and Yedavalli, {V. S.R.K.} and Jeang, {K. T.}",

note = "Funding Information: We thank A Dayton, J Ward, and members of the Jeang Laboratory for readings of manuscript; the NIAID core facility for MS-peptide sequencing; A Elmo for preparation of manuscript; and Y Li for technical assistance. This research was supported by the intramural research program of the NIAID, NIH.",

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AU - Haller, K.

AU - Kibler, K. V.

AU - Kasai, T.

AU - Chi, Y. H.

AU - Peloponese, J. M.

AU - Yedavalli, V. S.R.K.

AU - Jeang, K. T.

N1 - Funding Information: We thank A Dayton, J Ward, and members of the Jeang Laboratory for readings of manuscript; the NIAID core facility for MS-peptide sequencing; A Elmo for preparation of manuscript; and Y Li for technical assistance. This research was supported by the intramural research program of the NIAID, NIH.

PY - 2006/4/6

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N2 - The spindle assembly checkpoint (SAC) guards against chromosomal mis-segregation and the emergence of aneuploidy. SAC in higher eukaryotes includes at least 10 proteins including MAD1-3, BUB1-3, and Msp1. A long-standing observation has been that rodent cells are more tolerant of microtubule toxins than primate cells indicating that SAC function is more relaxed in the former than the latter. Here, we report on an unexpected functional difference between the rodent and human MAD1 component of the respective SAC. Ectopic expression of human MAD1 in mouse and hamster cells corrected a relaxed SAC to a more stringent form. Our findings posit MAD1 as a species-specific determinant which influences the stringency of cellular response to microtubule depolymerization and spindle damage.

AB - The spindle assembly checkpoint (SAC) guards against chromosomal mis-segregation and the emergence of aneuploidy. SAC in higher eukaryotes includes at least 10 proteins including MAD1-3, BUB1-3, and Msp1. A long-standing observation has been that rodent cells are more tolerant of microtubule toxins than primate cells indicating that SAC function is more relaxed in the former than the latter. Here, we report on an unexpected functional difference between the rodent and human MAD1 component of the respective SAC. Ectopic expression of human MAD1 in mouse and hamster cells corrected a relaxed SAC to a more stringent form. Our findings posit MAD1 as a species-specific determinant which influences the stringency of cellular response to microtubule depolymerization and spindle damage.

KW - Aneuploidy

KW - Cellular transformation

KW - Chromosomal instability

KW - Mitotic arrest

KW - Spindle assembly checkpoint

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The N-terminus of rodent and human MAD1 confers species-specific stringency to spindle assembly checkpoint

Abstract

Keywords

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