Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/80852
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dc.contributor.authorLim, Sai Kiangen
dc.contributor.authorTam, James P.en
dc.contributor.authorSze, Siu Kwanen
dc.contributor.authorDutta, Bamaprasaden
dc.contributor.authorYan, Renen
dc.date.accessioned2015-07-01T04:37:05Zen
dc.date.accessioned2019-12-06T14:15:53Z-
dc.date.available2015-07-01T04:37:05Zen
dc.date.available2019-12-06T14:15:53Z-
dc.date.copyright2014en
dc.date.issued2014en
dc.identifier.citationDutta, B., Yan, R., Lim, S. K., Tam, J. P., & Sze, S. K. (2014). Quantitative profiling of chromatome dynamics reveals a novel role for HP1BP3 in hypoxia-induced oncogenesis. Molecular & cellular proteomics, 13(12), 3236-3249.en
dc.identifier.urihttps://hdl.handle.net/10356/80852-
dc.description.abstractIn contrast to the intensely studied genetic and epigenetic changes that induce host cell transformation to initiate tumor development, those that promote the malignant progression of cancer remain poorly defined. As emerging evidence suggests that the hypoxic tumor microenvironment could re-model the chromatin-associated proteome (chromatome) to induce epigenetic changes and alter gene expression in cancer cells, we hypothesized that hypoxia-driven evolution of the chromatome promotes malignant changes and the development of therapy resistance in tumor cells. To test this hypothesis, we isolated chromatins from tumor cells treated with varying conditions of normoxia, hypoxia, and re-oxygenation and then partially digested them with DNase I and analyzed them for changes in euchromatin- and heterochromatin-associated proteins using an iTRAQ-based quantitative proteomic approach. We identified a total of 1446 proteins with a high level of confidence, including 819 proteins that were observed to change their chromatin association topology under hypoxic conditions. These hypoxia-sensitive proteins included key mediators of chromatin organization, transcriptional regulation, and DNA repair. Furthermore, our proteomic and functional experiments revealed a novel role for the chromatin organizer protein HP1BP3 in mediating chromatin condensation during hypoxia, leading to increased tumor cell viability, radio-resistance, chemo-resistance, and self-renewal. Taken together, our findings indicate that HP1BP3 is a key mediator of tumor progression and cancer cell acquisition of therapy-resistant traits, and thus might represent a novel therapeutic target in a range of human malignancies.en
dc.description.sponsorshipNMRC (Natl Medical Research Council, S’pore)en
dc.language.isoenen
dc.relation.ispartofseriesMolecular & cellular proteomicsen
dc.rights© 2014 American Society for Biochemistry and Molecular Biology. This is the author created version of a work that has been peer reviewed and accepted for publication by Molecular & Cellular Proteomics, American Society for Biochemistry and Molecular Biology. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1074/mcp.M114.038232].en
dc.subjectDRNTU::Science::Biological sciences::Molecular biologyen
dc.titleQuantitative profiling of chromatome dynamics reveals a novel role for HP1BP3 in hypoxia-induced oncogenesisen
dc.typeJournal Articleen
dc.contributor.schoolSchool of Biological Sciencesen
dc.identifier.doi10.1074/mcp.M114.038232en
dc.description.versionAccepted versionen
dc.identifier.pmid25100860-
item.grantfulltextopen-
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