The N-terminus of rodent and human MAD1 confers species-specific stringency to spindle assembly checkpoint.
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.
Haller
K
K
Molecular Virology Section, Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0460, USA.
Kibler
K V
KV
Kasai
T
T
Chi
Y-H
YH
Peloponese
J-M
JM
Yedavalli
V S R K
VS
Jeang
K-T
KT
D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D016466:CHO Cells / Q000187:drug effects / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D008938:Mitosis; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells / Q000187:drug effects / Q000378:metabolism; D015739:Nocodazole / Q000494:pharmacology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D008941:Spindle Apparatus
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; C501384:MAD1L1 protein, human; C501385:Mad1l1 protein, mouse; D009687:Nuclear Proteins; D015739:Nocodazole