PMID- 9859993 OWN - NLM STAT- MEDLINE DCOM- 19990107 LR - 20220408 IS - 0028-0836 (Print) IS - 0028-0836 (Linking) VI - 396 IP - 6711 DP - 1998 Dec 10 TI - Control of apoptosis and mitotic spindle checkpoint by survivin. PG - 580-4 AB - Progression of the cell cycle and control of apoptosis (programmed cell death) are thought to be intimately linked processes, acting to preserve homeostasis and developmental morphogenesis. Although proteins that regulate apoptosis have been implicated in restraining cell-cycle entry and controlling ploidy (chromosome number), the effector molecules at the interface between cell proliferation and cell survival have remained elusive. Here we show that a new inhibitor of apoptosis (IAP) protein, survivin, is expressed in the G2/M phase of the cell cycle in a cycle-regulated manner. At the beginning of mitosis, survivin associates with microtubules of the mitotic spindle in a specific and saturable reaction that is regulated by microtubule dynamics. Disruption of survivin-microtubule interactions results in loss of survivin's anti-apoptosis function and increased caspase-3 activity, a mechanism involved in cell death, during mitosis. These results indicate that survivin may counteract a default induction of apoptosis in G2/M phase. The overexpression of survivin in cancer may overcome this apoptotic checkpoint and favour aberrant progression of transformed cells through mitosis. FAU - Li, F AU - Li F AD - Boyer Center for Molecular Medicine, Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06536, USA. FAU - Ambrosini, G AU - Ambrosini G FAU - Chu, E Y AU - Chu EY FAU - Plescia, J AU - Plescia J FAU - Tognin, S AU - Tognin S FAU - Marchisio, P C AU - Marchisio PC FAU - Altieri, D C AU - Altieri DC LA - eng GR - 496/TI_/Telethon/Italy PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Nature JT - Nature JID - 0410462 RN - 0 (BIRC5 protein, human) RN - 0 (Inhibitor of Apoptosis Proteins) RN - 0 (Microtubule-Associated Proteins) RN - 0 (Neoplasm Proteins) RN - 0 (Proteins) RN - 0 (Survivin) RN - 0 (Tubulin) RN - 0 (Viral Proteins) RN - 0 (inhibitor of apoptosis, Nucleopolyhedrovirus) SB - IM MH - 3T3 Cells MH - Animals MH - Apoptosis/*physiology MH - Cell Cycle/physiology MH - G2 Phase/physiology MH - HeLa Cells MH - Humans MH - Inhibitor of Apoptosis Proteins MH - Mice MH - *Microtubule-Associated Proteins MH - Microtubules/physiology MH - Mitosis/physiology MH - Mutation MH - Neoplasm Proteins MH - Proteins/*physiology MH - Spindle Apparatus/*physiology MH - Survivin MH - Tubulin/physiology MH - Viral Proteins/genetics/physiology EDAT- 1998/12/22 03:04 MHDA- 2001/03/23 10:01 CRDT- 1998/12/22 03:04 PHST- 1998/12/22 03:04 [pubmed] PHST- 2001/03/23 10:01 [medline] PHST- 1998/12/22 03:04 [entrez] AID - 10.1038/25141 [doi] PST - ppublish SO - Nature. 1998 Dec 10;396(6711):580-4. doi: 10.1038/25141.