Survivin: Key Regulator of Mitosis and Apoptosis and Novel Target for Cancer Therapeutics

Survivin, a member of the family of inhibitor of apoptosis proteins, functions as a key regulator of mitosis and programmed cell death. Initially, survivin was described as an inhibitor of caspase-9. However, over the last years, research studies have shown that the role of survivin in cancer pathog...

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Bibliographic Details
Published in:Clinical cancer research 2008-08, Vol.14 (16), p.5000-5005
Main Authors: MITA, Alain C, MITA, Monica M, NAWROCKI, Steffan T, GILES, Francis J
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Antineoplastic Agents - pharmacology
Apoptosis - physiology
Biological and medical sciences
Humans
Inhibitor of Apoptosis Proteins
Medical sciences
Microtubule-Associated Proteins - physiology
Mitosis - physiology
Neoplasm Proteins - physiology
Neoplasms - drug therapy
Neoplasms - metabolism
Pharmacology. Drug treatments
Signal Transduction - physiology
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Summary:Survivin, a member of the family of inhibitor of apoptosis proteins, functions as a key regulator of mitosis and programmed cell death. Initially, survivin was described as an inhibitor of caspase-9. However, over the last years, research studies have shown that the role of survivin in cancer pathogenesis is not limited to apoptosis inhibition but also involves the regulation of the mitotic spindle checkpoint and the promotion of angiogenesis and chemoresistance. Survivin gene expression is transcriptionally repressed by wild-type p53 and can be deregulated in cancer by several mechanisms, including gene amplification, hypomethylation, increased promoter activity, and loss of p53 function. This article reviews the multiple functions of survivin in the regulation of apoptosis, the promotion of tumorigenesis, and the development of survivin inhibitors as a novel anticancer therapeutic strategy.
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.CCR-08-0746