| Proteomic profiling in distinct cellular compartments of tumor cells reveals p53-dependent upregulation of S100A6 upon induction of telomere dysfunction. | |
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MedLine Citation:
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PMID: 19834903 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Telomere dysfunction is evoking a DNA damage response which leads to replicative senescence or apoptosis. Tumor cells feature telomerase, a ribonucleoprotein complex counteracting telomere shortening and proliferation limitation as a prerequisite of immortal cell growth. Recently, we demonstrated the effects of telomerase inhibition on the proteome of tumor cell clones in whole cell lysates by SELDI-TOF-MS profiling and MS/MS protein identification (Zimmermann et al., Proteomics 2009, 9, 521-534). We continued proteomic analyses of such clones after telomerase-inhibition using fractionation of cellular compartments. Among the differentially expressed peaks found in different fractions, a cytoplasmic 10.1 kDa protein upregulated in telomerase-inhibited clones (p<0.0001) was identified by nanoflow-HPLC-MS/MS as S100A6. S100A6 upregulation was confirmed by immunoblotting in telomerase-inhibited HCT-116, A-549, and NCI-H460 clones. S100A6 and other proteins involved in telomere dysfunction were further analyzed in derivative p53(-/-) and p21(-/-) HCT-116 cell lines indicating an overall reduced number of significant changes in these lines compared to wild type HCT-116 cells. In addition, post-translational modification of S100A6 was demonstrated with a potential role in mediating the cellular response to telomere dysfunction. In conclusion, proteomic profiling in distinct cellular compartments led to the identification of a novel p53-dependent biomarker of telomere dysfunction, S100A6. |
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Authors:
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Stefan Zimmermann; Martin L Biniossek; Christian Maurer; Patrick M?nzer; Milena Pantic; Hendrik Veelken; Uwe M Martens |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Proteomics Volume: 9 ISSN: 1615-9861 ISO Abbreviation: Proteomics Publication Date: 2009 Nov |
Date Detail:
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Created Date: 2009-11-25 Completed Date: 2010-02-22 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101092707 Medline TA: Proteomics Country: Germany |
Other Details:
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Languages: eng Pagination: 5175-87 Citation Subset: IM |
Affiliation:
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University Medical Center Freiburg, Department of Hematology/Oncology, Hugstetter Strasse 55, Freiburg, Germany. stefan.zimmermann@uniklinik-freiburg.de |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cell Cycle Proteins
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metabolism* Cell Line, Tumor Gene Expression Profiling Humans Immunoblotting Immunoprecipitation Proteomics* S100 Proteins / metabolism* Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Telomerase / genetics, metabolism Telomere / metabolism* Tumor Suppressor Protein p53 / genetics, metabolism* Up-Regulation* |
| Chemical | |
Reg. No./Substance:
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0/Cell Cycle Proteins; 0/S100 Proteins; 0/Tumor Suppressor Protein p53; 105504-00-5/S100A6 protein, human; EC 2.7.7.49/Telomerase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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