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
