| Angiogenin functionally interacts with p53 and regulates p53-mediated apoptosis and cell survival. | |
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MedLine Citation:
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PMID: 22266868 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Angiogenin, a 14-kDa multifunctional pro-angiogenic growth factor, is upregulated in several types of cancers. Anti-angiogenin monoclonal antibodies used as antagonists inhibited the establishment, progression and metastasis of human cancer cells in athymic mice (Olson et al., 1994). Silencing angiogenin and inhibition of angiogenin's nuclear translocation blocked cell survival and induced cell death in B-lymphoma and endothelial cells latently infected with Kaposi sarcoma-associated herpesvirus (Sadagopan et al., 2009), suggesting that actively proliferating cancer cells could be inducing angiogenin for inhibiting apoptotic pathways. However, the mechanism of cell survival and apoptosis regulation by angiogenin and their functional significance in cancer is not known. We demonstrate that angiogenin interacts with p53 and colocalizes in the nucleus. Silencing endogenous angiogenin induced p53 promoter activation and p53 target gene (p53, p21 and Bax) expression, downregulated anti-apoptotic Bcl-2 gene expression and increased p53-mediated cell death. In contrast, angiogenin expression blocked pro-apoptotic Bax and p21 expression, induced Bcl-2 and blocked cell death. Angiogenin also co-immunoprecipitated with p53 regulator protein Mdm2. Angiogenin expression resulted in the inhibition of p53 phosphorylation, increased p53-Mdm2 interaction, and consequently increased ubiquitination of p53. Taken together, these studies demonstrate that angiogenin promotes the inhibition of p53 function to mediate anti-apoptosis and cell survival. Our results reveal for the first time a novel p53 interacting function of angiogenin in anti-apoptosis and survival of cancer cells and suggest that targeting angiogenin could be an effective therapy for several cancers. |
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Authors:
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S Sadagopan; M V Veettil; S Chakraborty; N Sharma-Walia; N Paudel; V Bottero; B Chandran |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-01-23 |
Journal Detail:
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Title: Oncogene Volume: 31 ISSN: 1476-5594 ISO Abbreviation: Oncogene Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-11-15 Completed Date: 2013-04-02 Revised Date: 2013-05-15 |
Medline Journal Info:
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Nlm Unique ID: 8711562 Medline TA: Oncogene Country: England |
Other Details:
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Languages: eng Pagination: 4835-47 Citation Subset: IM |
Affiliation:
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Department of Microbiology and Immunology, H.M. Bligh Cancer Research Laboratories, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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physiology* Cell Death / genetics Cell Nucleus / genetics, metabolism Cell Survival / physiology Cyclin-Dependent Kinase Inhibitor p21 / genetics, metabolism DNA-Binding Proteins / genetics, metabolism Down-Regulation Endothelial Cells / metabolism Gene Expression / genetics HCT116 Cells HeLa Cells Hep G2 Cells Humans Phosphorylation Promoter Regions, Genetic Protein Interaction Domains and Motifs Protein Structure, Tertiary Proto-Oncogene Proteins c-mdm2 / genetics, metabolism Ribonuclease, Pancreatic / metabolism* Tumor Suppressor Protein p53 / genetics, metabolism* Ubiquitination bcl-2-Associated X Protein / genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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AI 091767/AI/NIAID NIH HHS; R56 AI091767-01/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cyclin-Dependent Kinase Inhibitor p21; 0/DNA-Binding Proteins; 0/TP53 protein, human; 0/Tumor Suppressor Protein p53; 0/bcl-2-Associated X Protein; EC 3.1.27.-/angiogenin; EC 3.1.27.5/Ribonuclease, Pancreatic; EC 6.3.2.19/MDM2 protein, human; EC 6.3.2.19/Proto-Oncogene Proteins c-mdm2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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