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
Hypoxia 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...
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sg-ntu-dr.10356-1453462023-02-28T16:56:50Z 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 Park, Jung Eun Tse, Shun Wilford Xue, Guo Assisi, Christina Maqueda, Aida Serra Ramon, Gallart Palau Xavier Low, Jee Keem Kon, Oi Lian Tay, Chor Yong Tam, James P. Sze, Siu Kwan School of Biological Sciences School of Materials Science and Engineering Science::Biological sciences Hypoxia pSILAC Hypoxia 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. Ministry of Education (MOE) National Medical Research Council (NMRC) Published version This 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). 2020-12-17T09:20:45Z 2020-12-17T09:20:45Z 2019 Journal Article Park, 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.26669 1949-2553 https://hdl.handle.net/10356/145346 10.18632/oncotarget.26669 31040906 22 10 2136 2150 en MOE2014-T2-2-043 MOE2016-T2-2-018 MOE2016-T3-1-003 NMRC-OF-IRG-0003-2016 Oncotarget © 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. application/pdf |
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Science::Biological sciences Hypoxia pSILAC Park, Jung Eun Tse, Shun Wilford Xue, Guo Assisi, Christina Maqueda, Aida Serra Ramon, Gallart Palau Xavier Low, Jee Keem Kon, Oi Lian Tay, Chor Yong Tam, James P. Sze, Siu Kwan 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 |
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Hypoxia 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. |
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School of Biological Sciences |
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School of Biological Sciences Park, Jung Eun Tse, Shun Wilford Xue, Guo Assisi, Christina Maqueda, Aida Serra Ramon, Gallart Palau Xavier Low, Jee Keem Kon, Oi Lian Tay, Chor Yong Tam, James P. Sze, Siu Kwan |
format |
Article |
author |
Park, Jung Eun Tse, Shun Wilford Xue, Guo Assisi, Christina Maqueda, Aida Serra Ramon, Gallart Palau Xavier Low, Jee Keem Kon, Oi Lian Tay, Chor Yong Tam, James P. Sze, Siu Kwan |
author_sort |
Park, Jung Eun |
title |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
publishDate |
2020 |
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https://hdl.handle.net/10356/145346 |
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1759854544794157056 |