![[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}
|
|
|
|
|
||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Vol. 13, Issue 5, 1501-1511, May 2002
Department of Molecular Biology and Genetics, Cornell University,
Ithaca, New York 14853
The spindle checkpoint prevents anaphase from occurring until all
chromosomes have attached properly to the mitotic spindle. The
checkpoint components Mad1 and Mad2 associate with unattached kinetochores and are probably involved in triggering the
checkpoint. We now demonstrate that in Xenopus egg
extracts Mad1 and Mad2 form a stable complex, whereas a fraction of
Mad2 molecules is not bound to Mad1. The checkpoint establishment and
maintenance are lost upon titrating out free Mad2 with an excess of
Mad1 or a truncated Mad1 (amino acids 326-718, Mad1C) that contains
the Mad2-binding region. Mad1N (amino acids 1-445) that binds
kinetochores, but not Mad2, reduces Mad1 and Mad2 at
kinetochores and abolishes checkpoint maintenance.
Furthermore, the association between Mad2 and Cdc20, the activator for
the anaphase-promoting complex, is enhanced under
checkpoint-active condition compared with that at metaphase.
Immunodepletion analysis shows that the Mad1-free Mad2 protein is
unable to bind Cdc20, consistent with the model that
kinetochore localization of Mad2 facilitates the formation of Mad2-Cdc20 complex. This study demonstrates that the ratio between
Mad1 and Mad2 is critical for maintaining a pool of Mad1-free Mad2 that
is necessary for the spindle checkpoint. We propose that Mad2 may
become activated and dissociated from Mad1 at kinetochores and is replenished by the pool of Mad1-free Mad2.
This article has been cited by other articles:
|
|
 |
|
  J. Zhang, R. Neisa, and Y. Mao Oncogenic Adenomatous Polyposis Coli Mutants Impair the Mitotic Checkpoint through Direct Interaction with Mad2 Mol. Biol. Cell, May 1, 2009; 20(9): 2381 - 2388. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. P. De Souza, S. B. Hashmi, T. Nayak, B. Oakley, and S. A. Osmani Mlp1 Acts as a Mitotic Scaffold to Spatially Regulate Spindle Assembly Checkpoint Proteins in Aspergillus nidulans Mol. Biol. Cell, April 15, 2009; 20(8): 2146 - 2159. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Lince-Faria, S. Maffini, B. Orr, Y. Ding, Claudia Florindo, C. E. Sunkel, A. Tavares, J. Johansen, K. M. Johansen, and H. Maiato Spatiotemporal control of mitosis by the conserved spindle matrix protein Megator J. Cell Biol., March 9, 2009; 184(5): 647 - 657. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-H. Chi, K. Haller, M. D. Ward, O. J. Semmes, Y. Li, and K.-T. Jeang Requirements for Protein Phosphorylation and the Kinase Activity of Polo-like Kinase 1 (Plk1) for the Kinetochore Function of Mitotic Arrest Deficiency Protein 1 (Mad1) J. Biol. Chem., December 19, 2008; 283(51): 35834 - 35844. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M.-F. Sze, Y.-P. Ching, D.-Y. Jin, and I. O.-L. Ng Role of a Novel Splice Variant of Mitotic Arrest Deficient 1 (MAD1), MAD1{beta}, in Mitotic Checkpoint Control in Liver Cancer Cancer Res., November 15, 2008; 68(22): 9194 - 9201. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Bentley, G. Normand, J. Hoyt, and R. W. King Distinct Sequence Elements of Cyclin B1 Promote Localization to Chromatin, Centrosomes, and Kinetochores during Mitosis Mol. Biol. Cell, December 1, 2007; 18(12): 4847 - 4858. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Yu Structural activation of Mad2 in the mitotic spindle checkpoint: the two-state Mad2 model versus the Mad2 template model J. Cell Biol., April 24, 2006; 173(2): 153 - 157. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Daniel, B. E. Keyes, Y. P. Y. Ng, C. O. Freeman, and D. J. Burke Diverse Functions of Spindle Assembly Checkpoint Genes in Saccharomyces cerevisiae Genetics, January 1, 2006; 172(1): 53 - 65. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Kastenmayer, M. S. Lee, A. L. Hong, F. A. Spencer, and M. A. Basrai The C-Terminal Half of Saccharomyces cerevisiae Mad1p Mediates Spindle Checkpoint Function, Chromosome Transmission Fidelity and CEN Association Genetics, June 1, 2005; 170(2): 509 - 517. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. DeAntoni, V. Sala, and A. Musacchio Explaining the oligomerization properties of the spindle assembly checkpoint protein Mad2 Phil Trans R Soc B, March 29, 2005; 360(1455): 637 - 648. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Zhang, M. Li, W. Ma, Y. Hou, Y.-H. Li, S.-W. Li, Q.-Y. Sun, and W.-H. Wang Localization of Mitotic Arrest Deficient 1 (MAD1) in Mouse Oocytes During the First Meiosis and Its Functions as a Spindle Checkpoint Protein Biol Reprod, January 1, 2005; 72(1): 58 - 68. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Pati, B. R. Haddad, A. Haegele, H. Thompson, F. S. Kittrell, A. Shepard, C. Montagna, N. Zhang, G. Ge, S. K. Otta, et al. Hormone-Induced Chromosomal Instability in p53-Null Mammary Epithelium Cancer Res., August 15, 2004; 64(16): 5608 - 5616. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Pan and R.-H. Chen Spindle checkpoint regulates Cdc20p stability in Saccharomyces cerevisiae Genes & Dev., June 15, 2004; 18(12): 1439 - 1451. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. J. Tunquist, P. A. Eyers, L. G. Chen, A. L. Lewellyn, and J. L. Maller Spindle checkpoint proteins Mad1 and Mad2 are required for cytostatic factor-mediated metaphase arrest J. Cell Biol., December 22, 2003; 163(6): 1231 - 1242. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-H. Yih and T.-C. Lee Induction of C-Anaphase and Diplochromosome through Dysregulation of Spindle Assembly Checkpoint by Sodium Arsenite in Human Fibroblasts Cancer Res., October 15, 2003; 63(20): 6680 - 6688. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. S. Chun and D.-Y. Jin Transcriptional Regulation of Mitotic Checkpoint Gene MAD1 by p53 J. Biol. Chem., September 26, 2003; 278(39): 37439 - 37450. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. J. Tunquist and J. L. Maller Under arrest: cytostatic factor (CSF)-mediated metaphase arrest in vertebrate eggs Genes & Dev., March 15, 2003; 17(6): 683 - 710. [Full Text] [PDF]
|
|
|
|
 |
|
 L. Campbell and K. G. Hardwick Analysis of Bub3 spindle checkpoint function in Xenopus egg extracts J. Cell Sci., February 15, 2003; 116(4): 617 - 628. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Iouk, O. Kerscher, R. J. Scott, M. A. Basrai, and R. W. Wozniak The yeast nuclear pore complex functionally interacts with components of the spindle assembly checkpoint J. Cell Biol., December 9, 2002; 159(5): 807 - 819. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. B. Shannon, J. C. Canman, and E. D. Salmon Mad2 and BubR1 Function in a Single Checkpoint Pathway that Responds to a Loss of Tension Mol. Biol. Cell, October 1, 2002; 13(10): 3706 - 3719. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R.-H. Chen BubR1 is essential for kinetochore localization of other spindle checkpoint proteins and its phosphorylation requires Mad1 J. Cell Biol., August 5, 2002; 158(3): 487 - 496. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Canman, N. Sharma, A. Straight, K. B. Shannon, G. Fang, and E. D. Salmon Anaphase onset does not require the microtubule-dependent depletion of kinetochore and centromere-binding proteins J. Cell Sci., January 10, 2002; 115(19): 3787 - 3795. [Abstract] [Full Text] [PDF]
|
|
