Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/145346
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dc.contributor.authorPark, Jung Eunen_US
dc.contributor.authorTse, Shun Wilforden_US
dc.contributor.authorXue, Guoen_US
dc.contributor.authorAssisi, Christinaen_US
dc.contributor.authorMaqueda, Aida Serraen_US
dc.contributor.authorRamon, Gallart Palau Xavieren_US
dc.contributor.authorLow, Jee Keemen_US
dc.contributor.authorKon, Oi Lianen_US
dc.contributor.authorTay, Chor Yongen_US
dc.contributor.authorTam, James P.en_US
dc.contributor.authorSze, Siu Kwanen_US
dc.date.accessioned2020-12-17T09:20:45Z-
dc.date.available2020-12-17T09:20:45Z-
dc.date.issued2019-
dc.identifier.citationPark, J. E., Tse, S. W., Xue, G., Assisi, C., Maqueda, A. S., Ramon, G. P. X., . . . Sze, S. K. (2019). Pulsed SILAC-based proteomic analysis unveils hypoxia- and serum starvation-induced de novo protein synthesis with PHD finger protein 14 (PHF14) as a hypoxia sensitive epigenetic regulator in cell cycle progression. Oncotarget, 10(22), 2136-2150. doi:10.18632/oncotarget.26669en_US
dc.identifier.issn1949-2553en_US
dc.identifier.urihttps://hdl.handle.net/10356/145346-
dc.description.abstractHypoxia is an environmental cue that is associated with multiple tumorigenic processes such as immunosuppression, angiogenesis, cancer invasion, metastasis, drug resistance, and poor clinical outcomes. When facing hypoxic stress, cells initiate several adaptive responses such as cell cycle arrest to reduce excessive oxygen consumption and co-activation of oncogenic factors. In order to identify the critical novel proteins for hypoxia responses, we used pulsed-SILAC method to trace the active cellular translation events in A431 cells. Proteomic discovery data and biochemical assays showed that cancer cells selectively activate key glycolytic enzymes and novel ER-stress markers, while protein synthesis is severely suppressed. Interestingly, deprivation of oxygen affected the expression of various epigenetic regulators such as histone demethylases and NuRD (nucleosome remodeling and deacetylase) complex in A431 cells. In addition, we identified PHF14 (the plant homeodomain finger-14) as a novel hypoxia-sensitive epigenetic regulator that plays a key role in cell cycle progress and protein synthesis. Hypoxia-mediated inhibition of PHF14 was associated with increase of key cell cycle inhibitors, p14ARF, p15INK4b, and p16INK4a, which are responsible for G1-S phase transition and decrease of AKT-mTOR-4E-BP1/pS6K signaling pathway, a master regulator of protein synthesis, in response to environmental cues. Analysis of TCGA colon cancer (n=461) and skin cancer (n=470) datasets revealed a positive correlation between PHF14 expression and protein translation initiation factors, eIF4E, eIF4B, and RPS6. Significance of PHF14 gene was further demonstrated by in vivo mouse xenograft model using PHF14 KD cell lines.en_US
dc.description.sponsorshipMinistry of Education (MOE)en_US
dc.description.sponsorshipNational Medical Research Council (NMRC)en_US
dc.language.isoenen_US
dc.relationMOE2014-T2-2-043en_US
dc.relationMOE2016-T2-2-018en_US
dc.relationMOE2016-T3-1-003en_US
dc.relationNMRC-OF-IRG-0003-2016en_US
dc.relation.ispartofOncotargeten_US
dc.rights© 2019 Park et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.subjectScience::Biological sciencesen_US
dc.titlePulsed SILAC-based proteomic analysis unveils hypoxia- and serum starvation-induced de novo protein synthesis with PHD finger protein 14 (PHF14) as a hypoxia sensitive epigenetic regulator in cell cycle progressionen_US
dc.typeJournal Articleen
dc.contributor.schoolSchool of Biological Sciencesen_US
dc.contributor.schoolSchool of Materials Science and Engineeringen_US
dc.identifier.doi10.18632/oncotarget.26669-
dc.description.versionPublished versionen_US
dc.identifier.pmid31040906-
dc.identifier.issue22en_US
dc.identifier.volume10en_US
dc.identifier.spage2136en_US
dc.identifier.epage2150en_US
dc.subject.keywordsHypoxiaen_US
dc.subject.keywordspSILACen_US
dc.description.acknowledgementThis study was supported by the Singapore Ministry of Education (MOE2014-T2-2-043, MOE2016-T2-2-018 and MOE2016-T3-1-003) and the National Medical Research Council of Singapore (NMRC-OF-IRG-0003-2016).en_US
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