Regulation of apoptosis at cell division by p34cdc2 phosphorylation of survivin

AUTOR(ES)

O'Connor, Daniel S.

FONTE

The National Academy of Sciences

RESUMO

The interface between apoptosis (programmed cell death) and the cell cycle is essential to preserve homeostasis and genomic integrity. Here, we show that survivin, an inhibitor of apoptosis over-expressed in cancer, physically associates with the cyclin-dependent kinase p34cdc2 on the mitotic apparatus, and is phosphorylated on Thr34 by p34cdc2-cyclin B1, in vitro and in vivo. Loss of phosphorylation on Thr34 resulted in dissociation of a survivin-caspase-9 complex on the mitotic apparatus, and caspase-9-dependent apoptosis of cells traversing mitosis. These data identify survivin as a mitotic substrate of p34cdc2-cyclin B1 and suggest that survivin phosphorylation on Thr34 may be required to preserve cell viability at cell division. Manipulation of this pathway may facilitate the elimination of cancer cells at mitosis.

Documentos Relacionados

• Mechanisms of p34cdc2 regulation.
• Cell cycle regulation of the p34cdc2 inhibitory kinases.
• Mitosis-specific phosphorylation of nucleolin by p34cdc2 protein kinase.
• Cyclin B targets p34cdc2 for tyrosine phosphorylation.
• Phosphorylation at Thr167 is required for Schizosaccharomyces pombe p34cdc2 function.