Regulation of apoptosis at cell division by p34(cdc2) phosphorylation of survivin

Citation
Ds. O'Connor et al., Regulation of apoptosis at cell division by p34(cdc2) phosphorylation of survivin, P NAS US, 97(24), 2000, pp. 13103-13107
Citations number
31
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN journal
0027-8424 → ACNP
Volume
97
Issue
24
Year of publication
2000
Pages
13103 - 13107
Database
ISI
SICI code
0027-8424(20001121)97:24<13103:ROAACD>2.0.ZU;2-G
Abstract
The interface between apoptosis (programmed cell death) and the cell cycle is essential to preserve homeostasis and genomic integrity. Here, we show t hat survivin, an inhibitor of apoptosis over-expressed in cancer, physicall y associates with the cyclin-dependent kinase p34(cdc2) On the mitotic appa ratus, and is phosphorylated on Thr(34) by p34(cdc2)-cyclin B1, in vitro an d in vivo. Loss of phosphorylation on Thr34 resulted in dissociation of a s urvivin-caspase-9 complex on the mitotic apparatus, and caspase-9-dependent apoptosis of cells traversing mitosis. These data identify survivin as a m itotic substrate of p34(cdc2)-cyclin B1 and suggest that survivin phosphory lation on Thr(34) may be required to preserve cell viability at cell divisi on. Manipulation of this pathway may facilitate the elimination of cancer c ells at mitosis.