Table 1.
Effects of partial inactivation of spindle checkpoint and overexpression of checkpoint proteins on sensitivity to treatment with antimitotic drugs
| Modulation on spindle checkpoint | Effect on spindle checkpoint function | Antimitotic drug tested | Drug sensitivity | Assay* | Assay length (h) | Reference |
|---|---|---|---|---|---|---|
| Cancer cell line variants |
Weakened | Nocodazole | Decreased | A, B | 48 | Masuda et al. (50) |
| Cancer cell lines | Weakened | Nocodazole | Increased | C, E | 48 | Lee et al. (13) |
| varying in BubR1 | Taxol | Increased | C, E | |||
| expression | ||||||
| Human T-cell leukemia | Weakened | Nocodazole | Decreased | F | 24–48 | Kasai et al. (52) |
| virus type I infection | Vincristine | Decreased | F | |||
| (Mad1 inactivation) | ||||||
| BubR1-siRNA | Weakened | Taxol | Decreased | D, F | 48 | |
| Mad2-siRNA | Weakened | Taxol | Decreased | D, F | 48 | Sudo et al. (53) |
| dnBub1 | Weakened | KSP-IA | Decreased | B, C, E | 48 | Tao et al. (5) |
| Taxol | Decreased (mildly) | B, C, E | ||||
| Mad2 haploinsufficiency | Weakened | KSP-IA | Decreased | B, C, E | ||
| Taxol | Decreased (mildly) | B, C, E | ||||
| Mad1-siRNA | Weakened | Nocodazole | Decreased | A, B | 40–48 | Kienitz et al. (54) |
| Taxol | Unchanged | A, B | ||||
| Monastrol | Unchanged | A, B | ||||
| Mad2 haploinsufficiency | Weakened | Nocodazole | Decreased | A, B | ||
| Taxol | Decreased | A, B | ||||
| Monastrol | Decreased | A, B | ||||
| Mad2 overexpression | Strengthened | Vincristine | Increased | A, C, G | A—72 | Wang et al. (55) |
| Taxol | Unchanged | A, C, G | C—96 | |||
| G—12 days | ||||||
| Mad2 overexpression in Mad2-siRNA |
Weakened then restored | Taxol | Increased | D | 48 | Sudo et al. (53) |
| Mad2 overexpression in BubR1-siRNA |
Weakened | Taxol | Unchanged | D | ||
| Overexpression of | ||||||
| BubR1 | Not determined | Nocodazole | Increased | B, C | 48–96 | Shin et al. (44) |
| Bub1 | Nocodazole | Increased (mildly) | B, C | |||
| Mad1 | Nocodazole | Unchanged | B, C | |||
| Mad2 | Nocodazole | Unchanged | B, C | |||
| Bub3 | Nocodazole | Unchanged | B, C |
*
“Short-term” assays: A, DNA fragmentation; B, caspase 3 activation, poly-ADP-ribose polymerase fragment generation; C, appearance of sub-G1 peak in fluorescence-activated cell sorting; D, trypan blue exclusion; E, colony formation assay after short drug exposure; F, cellular metabolism [e.g., 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]. “Long-term” assays: G, colony formation assay in continuous presence of drug.