| Survivin and escaping in therapy-induced cellular senescence. | |
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MedLine Citation:
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PMID: 20503268 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Therapy-induced accelerated cellular senescence (ACS) is a reversible tumor response to chemotherapy that is likely detrimental to the overall therapeutic efficacy of cancer treatment. To further understand the mechanism by which cancer cells can escape the sustained cell cycle arrest in ACS, we established a tissue culture model, in which the p53-null NCI-H1299 cells can be induced into senescence by an abbreviated exposure to a chemotherapeutic agent. Previously, we have reported that senescent cells overexpress Cdc2/Cdk1 when they bypassed the prolonged arrest and their viability is dependent on Cdc2/Cdk1 kinase activity. In our study, we show that human survivin is the immediate downstream effector of the Cdc2/Cdk1 mediated survival signal. Survivin cooperates with Cdc2/Cdk1 to inhibit apoptosis following chemotherapy and promote senescence escape. Using HIV-1 TAT peptides to disrupt survivin phosphorylation by Cdc2/Cdk1, we also found that phosphorylated survivin is necessary both for the escape of senescent cells and for maintenance of subsequent viability after bypassing senescence. These results further propose survivin as an important determinant of senescence reversibility and as a putative molecular target to enforce cell death in ACS. |
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Authors:
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Qin Wang; Peter C Wu; Rachel S Roberson; Belinda V Luk; Iana Ivanova; Elizabeth Chu; Daniel Y Wu |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-05-25 |
Journal Detail:
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Title: International journal of cancer. Journal international du cancer Volume: 128 ISSN: 1097-0215 ISO Abbreviation: Int. J. Cancer Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-01-31 Completed Date: 2011-04-04 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 0042124 Medline TA: Int J Cancer Country: United States |
Other Details:
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Languages: eng Pagination: 1546-58 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 UICC. |
Affiliation:
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Seattle Institute for Biomedical and Clinical Research, VA Puget Sound Health Care System, Seattle, Washington. proteinss@hotmail.com |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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pharmacology Apoptosis CDC2 Protein Kinase / metabolism Cell Aging* Cell Line, Tumor Cyclin B / metabolism Gene Products, tat / metabolism Humans Microtubule-Associated Proteins / metabolism* Oligonucleotides, Antisense / chemistry Phosphorylation RNA, Small Interfering / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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R01 CA113892-01A1/CA/NCI NIH HHS; R01-CA113892-01/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/BIRC5 protein, human; 0/CDC2 protein, human; 0/Cyclin B; 0/Gene Products, tat; 0/Microtubule-Associated Proteins; 0/Oligonucleotides, Antisense; 0/RNA, Small Interfering; EC 2.7.11.22/CDC2 Protein Kinase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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