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Science 16 July 1999:
Vol. 285. no. 5426, pp. 418 - 422
DOI: 10.1126/science.285.5426.418
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Reports

Identification of a Vertebrate Sister-Chromatid Separation Inhibitor Involved in Transformation and Tumorigenesis

Hui Zou, Thomas J. McGarry, Teresita Bernal, Marc W. Kirschner *

A vertebrate securin (vSecurin) was identified on the basis of its biochemical analogy to the Pds1p protein of budding yeast and the Cut2p protein of fission yeast. The vSecurin protein bound to a vertebrate homolog of yeast separins Esp1p and Cut1p and was degraded by proteolysis mediated by an anaphase-promoting complex in a manner dependent on a destruction motif. Furthermore, expression of a stable Xenopus securin mutant protein blocked sister-chromatid separation but did not block the embryonic cell cycle. The vSecurin proteins share extensive sequence similarity with each other but show no sequence similarity to either of their yeast counterparts. Human securin is identical to the product of the gene called pituitary tumor-transforming gene (PTTG), which is overexpressed in some tumors and exhibits transforming activity in NIH 3T3 cells. The oncogenic nature of increased expression of vSecurin may result from chromosome gain or loss, produced by errors in chromatid separation.

Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
*   To whom correspondence should be addressed. E-mail: marc{at}hms.harvard.edu

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N. Pedersen, S. Mortensen, S. B. Sorensen, M. W. Pedersen, K. Rieneck, L. F. Bovin, and H. S. Poulsen (2003)
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   Abstract »    Full Text »    PDF »
Processing, localization, and requirement of human separase for normal anaphase progression.
A. Chestukhin, C. Pfeffer, S. Milligan, J. A. DeCaprio, and D. Pellman (2003)
PNAS 100, 4574-4579
   Abstract »    Full Text »    PDF »
Human Pituitary Tumor-Transforming Gene (PTTG1) Motif Suppresses Prolactin Expression.
G. A. Horwitz, I. Miklovsky, A. P. Heaney, S.-G. Ren, and S. Melmed (2003)
Mol. Endocrinol. 17, 600-609
   Abstract »    Full Text »    PDF »
Pituitary tumor transforming gene-null male mice exhibit impaired pancreatic beta cell proliferation and diabetes.
Z. Wang, E. Moro, K. Kovacs, R. Yu, and S. Melmed (2003)
PNAS 100, 3428-3432
   Abstract »    Full Text »    PDF »
Analysis of Bub3 spindle checkpoint function in Xenopus egg extracts.
L. Campbell and K. G. Hardwick (2003)
J. Cell Sci. 116, 617-628
   Abstract »    Full Text »    PDF »
DNA Damage-induced Inhibition of Securin Expression Is Mediated by p53.
Y. Zhou, K. R. Mehta, A. P. Choi, S. Scolavino, and X. Zhang (2003)
J. Biol. Chem. 278, 462-470
   Abstract »    Full Text »    PDF »
Linking Sister Chromatid Cohesion and Apoptosis: Role of Rad21.
D. Pati, N. Zhang, and S. E. Plon (2002)
Mol. Cell. Biol. 22, 8267-8277
   Abstract »    Full Text »    PDF »
Meiotic Cohesion Requires Accumulation of ORD on Chromosomes before Condensation.
E. M. Balicky, M. W. Endres, C. Lai, and S. E. Bickel (2002)
Mol. Biol. Cell 13, 3890-3900
   Abstract »    Full Text »    PDF »
Attachment and tension in the spindle assembly checkpoint.
J. Zhou, J. Yao, and H. C. Joshi (2002)
J. Cell Sci. 115, 3547-3555
   Abstract »    Full Text »    PDF »
Proteolytic cleavage of the THR subunit during anaphase limits Drosophila separase function.
A. Herzig, C. F. Lehner, and S. Heidmann (2002)
Genes & Dev. 16, 2443-2454
   Abstract »    Full Text »    PDF »
The anaphase-promoting complex: it's not just for mitosis any more.
J. W. Harper, J. L. Burton, and M. J. Solomon (2002)
Genes & Dev. 16, 2179-2206
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Noscapine Alters Microtubule Dynamics in Living Cells and Inhibits the Progression of Melanoma.
J. W. Landen, R. Lang, S. J. McMahon, N. M. Rusan, A.-M. Yvon, A. W. Adams, M. D. Sorcinelli, R. Campbell, P. Bonaccorsi, J. C. Ansel, et al. (2002)
Cancer Res. 62, 4109-4114
   Abstract »    Full Text »    PDF »
Expression of PTTG (Pituitary Tumor Transforming Gene) in Esophageal Cancer.
Y. Shibata, N. Haruki, Y. Kuwabara, T. Nishiwaki, J. Kato, N. Shinoda, A. Sato, M. Kimura, H. Koyama, T. Toyama, et al. (2002)
Jpn. J. Clin. Oncol. 32, 233-237
   Abstract »    Full Text »    PDF »
Human securin proteolysis is controlled by the spindle checkpoint and reveals when the APC/C switches from activation by Cdc20 to Cdh1.
A. Hagting, N. den Elzen, H. C. Vodermaier, I. C. Waizenegger, J.-M. Peters, and J. Pines (2002)
J. Cell Biol. 157, 1125-1137
   Abstract »    Full Text »    PDF »


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