![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
RESEARCH PAPER
Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA
The spindle checkpoint arrests cells at the metaphase-to-anaphase transition until all chromosomes have properly attached to the mitotic spindle. Checkpoint proteins Mad2p and Mad3p/BubR1p bind and inhibit Cdc20p, an activator for the anaphase-promoting complex (APC). We find that upon spindle checkpoint activation by microtubule inhibitors benomyl or nocodazole, wild-type Saccharomyces cerevisiae contains less Cdc20p than spindle checkpoint mutants do, whereas their CDC20 mRNA levels are similar. The difference in Cdc20p levels correlates with their difference in the half-lives of Cdc20p, indicating that the spindle checkpoint destabilizes Cdc20p. This process requires the association between Cdc20p and Mad2p, and functional APC, but is independent of the known destruction boxes in Cdc20p and the other APC activator Cdh1p. Importantly, destabilization of Cdc20p is important for the spindle checkpoint, because a modest overexpression of Cdc20p causes benomyl sensitivity and premature Pds1p degradation in cells treated with nocodazole. Our study suggests that the spindle checkpoint reduces Cdc20p to below a certain threshold level to ensure a complete inhibition of Cdc20p before anaphase.
[Keywords: Spindle checkpoint; Cdc20p; Mad2p; kinetochore; protein stability]
Received January 6, 2004; revised version accepted April 22, 2004.
1 Present address: Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan.
2 Corresponding author. E-MAIL rc70{at}cornell.edu; FAX (607) 255-6249.
CiteULike 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Baskerville, M. Segal, and S. I. Reed The Protease Activity of Yeast Separase (Esp1) Is Required for Anaphase Spindle Elongation Independently of Its Role In Cleavage of Cohesin Genetics, April 1, 2008; 178(4): 2361 - 2372. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. E. Keyes, C. M. Yellman, and D. J. Burke Differential Regulation of Anaphase Promoting Complex/Cyclosome Substrates by the Spindle Assembly Checkpoint in Saccharomyces cerevisiae Genetics, January 1, 2008; 178(1): 589 - 591. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Burton and M. J. Solomon Mad3p, a pseudosubstrate inhibitor of APCCdc20 in the spindle assembly checkpoint Genes & Dev., March 15, 2007; 21(6): 655 - 667. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Mondal, S. Sengupta, C. K. Panda, S. M. Gollin, W. S. Saunders, and S. Roychoudhury Overexpression of Cdc20 leads to impairment of the spindle assembly checkpoint and aneuploidization in oral cancer Carcinogenesis, January 1, 2007; 28(1): 81 - 92. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. R. Thornton and D. P. Toczyski Precise destruction: an emerging picture of the APC. Genes & Dev., November 15, 2006; 20(22): 3069 - 3078. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. P. Sear and M. Howard Modeling dual pathways for the metazoan spindle assembly checkpoint PNAS, November 7, 2006; 103(45): 16758 - 16763. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. May and K. G. Hardwick The spindle checkpoint J. Cell Sci., October 15, 2006; 119(20): 4139 - 4142. [Full Text] [PDF]
|
|
|
|
 |
|
 W. J. Palframan, J. B. Meehl, S. L. Jaspersen, M. Winey, and A. W. Murray Anaphase Inactivation of the Spindle Checkpoint Science, August 4, 2006; 313(5787): 680 - 684. [Abstract] [Full Text] [PDF]
|
|
