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https://hdl.handle.net/2440/59518
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Type: | Journal article |
Title: | A tumor suppressor function for caspase-2 |
Author: | Ho, L. Taylor, R. Dorstyn, L. Cakouros, D. Bouillet, P. Kumar, S. |
Citation: | Proceedings of the National Academy of Sciences of USA, 2009; 106(13):5336-5341 |
Publisher: | Natl Acad Sciences |
Issue Date: | 2009 |
ISSN: | 0027-8424 1091-6490 |
Statement of Responsibility: | Lien Ha Ho, Robyn Taylor, Loretta Dorstyn, Dimitrios Cakouros, Philippe Bouillet and Sharad Kumar |
Abstract: | Apoptosis is mediated by the caspase family of proteases that act as effectors of cell death by cleaving many cellular substrates. Caspase-2 is one of the most evolutionarily conserved caspases, yet its physiological function has remained enigmatic because caspase-2-deficient mice develop normally and are viable. We report here that the caspase-2−/− mouse embryonic fibroblasts (MEFs) show increased proliferation. When transformed with E1A and Ras oncogenes, caspase-2−/− MEFs grew significantly faster than caspase-2+/+ MEFs and formed more aggressive and accelerated tumors in nude mice. To assess whether the loss of caspase-2 predisposes animals to tumor development, we used the mouse Eμ-Myc lymphoma model. Our findings suggest that loss of even a single allele of caspase-2 resulted in accelerated tumorigenesis, and this was further enhanced in caspase-2−/− mice. The caspase-2−/− cells showed resistance to apoptosis induced by chemotherapeutic drugs and DNA damage. Furthermore, caspase-2−/− MEFs had a defective apoptotic response to cell-cycle checkpoint regulation and showed abnormal cycling following γ-irradiation. These data show that loss of caspase-2 results in an increased ability of cells to acquire a transformed phenotype and become malignant, indicating that caspase-2 is a tumor suppressor protein. |
Keywords: | cell survival tumorigenesis cell cycle proliferation DNA damage |
Rights: | © Authors |
DOI: | 10.1073/pnas.0811928106 |
Published version: | http://dx.doi.org/10.1073/pnas.0811928106 |
Appears in Collections: | Aurora harvest 5 Medicine publications |
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