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PMID: 11069302 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Regulation of apoptosis at cell division by p34cdc2 phosphorylation of survivin.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 97 ·No. 24 ·2000-11-21 ·Pages 13103-7

O'Connor DS, Grossman D, Plescia J, Li F, Zhang H, Villa A, Tognin S, Marchisio PC, Altieri DC

Abstract

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 p34(cdc2) on the mitotic apparatus, and is phosphorylated on Thr(34) by p34(cdc2)-cyclin B1, in vitro and in vivo. Loss of phosphorylation on Thr(34) 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 p34(cdc2)-cyclin B1 and suggest that survivin phosphorylation on Thr(34) may be required to preserve cell viability at cell division. Manipulation of this pathway may facilitate the elimination of cancer cells at mitosis.

MeSH Terms
Amino Acid Sequence Antibodies Apoptosis/physiology CDC2 Protein Kinase/metabolism Cell Cycle/physiology Cell Division/physiology HeLa Cells Humans Inhibitor of Apoptosis Proteins Kinetics Melanoma Microtubule-Associated Proteins Molecular Sequence Data Mutagenesis, Site-Directed Neoplasm Proteins Peptide Fragments/chemistry,immunology,metabolism Phosphorylation Proteins/chemistry,genetics,metabolism Recombinant Proteins/chemistry,metabolism Survivin Transfection Tumor Cells, Cultured
Chemicals
Antibodies BIRC5 protein, human Inhibitor of Apoptosis Proteins Microtubule-Associated Proteins Neoplasm Proteins Peptide Fragments Proteins Recombinant Proteins Survivin CDC2 Protein Kinase
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
O'Connor D S
Departments of Pathology, Dermatology, and Genetics, Boyer Center for Molecular Medicine, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.
Grossman D
Plescia J
Li F
Zhang H
Villa A
Tognin S
Marchisio P C
Altieri D C
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.240390697
Published
2000-11-21
Pages
13103-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC27185
Subset
IM
Grants
NCI NIH HHS · R01 CA078810 · United States
NCI NIH HHS · CA78810 · United States
NHLBI NIH HHS · R37 HL054131 · United States
NIAMS NIH HHS · T32 AR007016 · United States
NHLBI NIH HHS · HL54131 · United States
NCI NIH HHS · CA72878 · United States
NHLBI NIH HHS · R01 HL054131 · United States
External Links
PubMed source DOI: 10.1073/pnas.240390697 PMC Full Text View journal details
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