Mechanisms of Caspase-3 Regulation in the Execution of Cell Death
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The Ohio State University / OhioLINK
2012
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| Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=osu1331142346 |
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ndltd-OhioLink-oai-etd.ohiolink.edu-osu13311423462021-08-03T06:04:48Z Mechanisms of Caspase-3 Regulation in the Execution of Cell Death Malavez, Yadira Molecular Biology Apoptosis Cell death Caspase-3 PKCd Proein Kinase C delta phosphorylation mutagenesis <p>Apoptosis is an evolutionarily conserved mechanism necessary for the homeostasis in multicellular organisms. The cysteine protease caspase-3 has a key role in apoptosis for its central role in the execution of the apoptotic cascade. The molecular mechanisms that regulate caspase-3 activation are not completely understood. Previously, our laboratory demonstrated that caspase-3 is phosphorylated by PKCδ in human monocytes. However, the role of caspase-3 phosphorylation during apoptosis has not been elucidated. In this investigation, it was observed that PKCδ is necessary for caspase-3 phosphorylation. An interaction motif in caspase-3 was identified to be necessary for PKCδ interaction. Five PKCδ phosphorylated sites in caspase-3 were mapped utilizing mass spectroscopy. Phosphorylation of specific sites promoted caspase-3 autocatalytic cleavage and apoptosis, in vitro and in vivo. Caspase-3 phosphorylation acts in a positive feedback mechanism to amplify the apoptotic cascade. These results suggest a novel regulatory mechanism to control caspase-3 apoptotic activity and execution of cell death. </p><p>Furthermore, the apoptotic and immunological heterogeneity in CD14+CD16+ and CD14+CD16- monocytes was analyzed. It was observed that CD14+CD16+ cells were more susceptible to undergo spontaneous apoptosis, in part due to upregulation of the activity of the caspases. CD14+CD16+ monocytes release more TNF-α compared to the CD14+CD16- counterparts. Furthermore, the expression of the members of the PKC family was characterized in monocyte subsets. These results suggested that elevated expression of PKCε may play a role in the pro-inflammatory role of CD14+CD16+ monocytes. The current investigation highlights the importance of caspase-3 and the members of the PKC family as important regulators of cell death and survival pathways.</p> 2012-06-19 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1331142346 http://rave.ohiolink.edu/etdc/view?acc_num=osu1331142346 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
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NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Molecular Biology Apoptosis Cell death Caspase-3 PKCd Proein Kinase C delta phosphorylation mutagenesis |
| spellingShingle |
Molecular Biology Apoptosis Cell death Caspase-3 PKCd Proein Kinase C delta phosphorylation mutagenesis Malavez, Yadira Mechanisms of Caspase-3 Regulation in the Execution of Cell Death |
| author |
Malavez, Yadira |
| author_facet |
Malavez, Yadira |
| author_sort |
Malavez, Yadira |
| title |
Mechanisms of Caspase-3 Regulation in the Execution of Cell Death |
| title_short |
Mechanisms of Caspase-3 Regulation in the Execution of Cell Death |
| title_full |
Mechanisms of Caspase-3 Regulation in the Execution of Cell Death |
| title_fullStr |
Mechanisms of Caspase-3 Regulation in the Execution of Cell Death |
| title_full_unstemmed |
Mechanisms of Caspase-3 Regulation in the Execution of Cell Death |
| title_sort |
mechanisms of caspase-3 regulation in the execution of cell death |
| publisher |
The Ohio State University / OhioLINK |
| publishDate |
2012 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=osu1331142346 |
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AT malavezyadira mechanismsofcaspase3regulationintheexecutionofcelldeath |
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1719430524457451520 |