dc.contributor.author | Pavlou, Demos | en |
dc.contributor.author | Kirmizis, Antonis | en |
dc.creator | Pavlou, Demos | en |
dc.creator | Kirmizis, Antonis | en |
dc.date.accessioned | 2019-11-04T12:52:28Z | |
dc.date.available | 2019-11-04T12:52:28Z | |
dc.date.issued | 2016 | |
dc.identifier.issn | 1360-8185 | |
dc.identifier.uri | http://gnosis.library.ucy.ac.cy/handle/7/53296 | |
dc.description.abstract | Protein N-terminal acetylation is an abundant post-translational modification in eukaryotes implicated in various fundamental cellular and biochemical processes. This modification is catalysed by evolutionarily conserved N-terminal acetyltransferases (NATs) whose deregulation has been linked to cancer development and thus, are emerging as useful diagnostic and therapeutic targets. Naa40 is a highly selective NAT that acetylates the amino-termini of histones H4 and H2A and acts as a sensor of cell growth in yeast. In the present study, we examine the role of Naa40 in cancer cell survival. We demonstrate that depletion of Naa40 in HCT116 and HT-29 colorectal cancer cells decreases cell survival by enhancing apoptosis, whereas Naa40 reduction in non-cancerous mouse embryonic fibroblasts has no effect on cell viability. Specifically, Naa40 knockdown in colon cancer cells activates the mitochondrial caspase-9-mediated apoptotic cascade. Consistent with this, we show that caspase-9 activation is required for the induced apoptosis because treatment of cells with an irreversible caspase-9 inhibitor impedes apoptosis when Naa40 is depleted. Furthermore, the effect of Naa40-depletion on cell-death is mediated through a p53-independent mechanism since p53-null HCT116 cells still undergo apoptosis upon reduction of the acetyltransferase. Altogether, these findings reveal an anti-apoptotic role for Naa40 and exhibit its potential as a therapeutic target in colorectal cancers. © The Author(s) 2015. | en |
dc.source | Apoptosis | en |
dc.source.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84957439440&doi=10.1007%2fs10495-015-1207-0&partnerID=40&md5=d608d0b72a6c38c770be71a380abf93b | |
dc.subject | human | en |
dc.subject | Humans | en |
dc.subject | controlled study | en |
dc.subject | priority journal | en |
dc.subject | protein p53 | en |
dc.subject | Tumor Suppressor Protein p53 | en |
dc.subject | unclassified drug | en |
dc.subject | Colorectal cancer | en |
dc.subject | Colorectal Neoplasms | en |
dc.subject | carcinogenesis | en |
dc.subject | pathology | en |
dc.subject | signal transduction | en |
dc.subject | Article | en |
dc.subject | metabolism | en |
dc.subject | cancer cell | en |
dc.subject | Apoptosis | en |
dc.subject | human cell | en |
dc.subject | gene expression | en |
dc.subject | Animals | en |
dc.subject | Mice | en |
dc.subject | animal | en |
dc.subject | cell survival | en |
dc.subject | mouse | en |
dc.subject | genetics | en |
dc.subject | small interfering RNA | en |
dc.subject | physiology | en |
dc.subject | colorectal tumor | en |
dc.subject | gene silencing | en |
dc.subject | fibroblast | en |
dc.subject | cell viability | en |
dc.subject | caspase 9 | en |
dc.subject | HT29 Cells | en |
dc.subject | protein processing | en |
dc.subject | Caspase Inhibitors | en |
dc.subject | RNA, Small Interfering | en |
dc.subject | Mitochondria | en |
dc.subject | mitochondrion | en |
dc.subject | caspase inhibitor | en |
dc.subject | Protein Processing, Post-Translational | en |
dc.subject | Histones | en |
dc.subject | histone | en |
dc.subject | Gene Knockdown Techniques | en |
dc.subject | acetylation | en |
dc.subject | acyltransferase | en |
dc.subject | N-Terminal Acetyltransferase D | en |
dc.subject | peptide alpha n acetyltransferase D | en |
dc.subject | protein acetylation | en |
dc.subject | Epigenetics | en |
dc.subject | CASP9 protein, human | en |
dc.subject | cell activation | en |
dc.subject | HCT 116 cell line | en |
dc.subject | HCT116 Cells | en |
dc.subject | histone n terminal acetyltransferase naa40 | en |
dc.subject | Histone N-terminal acetylation | en |
dc.subject | HT-29 cell line | en |
dc.subject | Naa40 | en |
dc.subject | NAA40 protein, human | en |
dc.subject | NatD | en |
dc.subject | TP53 protein, human | en |
dc.title | Depletion of histone N-terminal-acetyltransferase Naa40 induces p53-independent apoptosis in colorectal cancer cells via the mitochondrial pathway | en |
dc.type | info:eu-repo/semantics/article | |
dc.identifier.doi | 10.1007/s10495-015-1207-0 | |
dc.description.volume | 21 | |
dc.description.startingpage | 298 | |
dc.description.endingpage | 311 | |
dc.author.faculty | Σχολή Θετικών και Εφαρμοσμένων Επιστημών / Faculty of Pure and Applied Sciences | |
dc.author.department | Τμήμα Βιολογικών Επιστημών / Department of Biological Sciences | |
dc.type.uhtype | Article | en |
dc.description.notes | <p>Cited By :4</p> | en |
dc.source.abbreviation | Apoptosis | en |
dc.contributor.orcid | Kirmizis, Antonis [0000-0002-3748-8711] | |
dc.gnosis.orcid | 0000-0002-3748-8711 | |