Issue |
E3S Web Conf.
Volume 271, 2021
2021 2nd International Academic Conference on Energy Conservation, Environmental Protection and Energy Science (ICEPE 2021)
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Article Number | 03017 | |
Number of page(s) | 9 | |
Section | Research on Energy Chemistry and Chemical Simulation Performance | |
DOI | https://doi.org/10.1051/e3sconf/202127103017 | |
Published online | 15 June 2021 |
Studying potential PKCδ loss of function mutation and its downstream effects in gastric cancer progression
RMIT, Melbourne, Australia
PKC isozymes are involved in the modulation of cellular pathways related with tumor progression, acting as a suppressor or promoter. In cancer cells, PKCs are mutated, and most common type is loss of function. This paper focuses on the effect of PKCδ mutation in gastric cancer. LOF mutation occurs throughout catalytic and kinase domains of PKCδ, disrupting activation and function of kinase. In catalytic domain, there are various potential mutation targets, such as binding groove and zinc finger. Mutation residues detected in the kinase domain, such as DFG and APE motifs, can alter catalytic function, causing interruption of activation. Also, a critical region, called hinge region, modulates caspase-3 dependent cleavage, and such tyrosine mutation in this region reduces cleavage activity, inhibiting fully activation of kinase. Importantly, LOF mutation affects cellular activity of downstream protein, p53, through inhibiting transcription, localization, and phosphorylation. For instance, C1 domain mutant suppresses binding capacity with p53, reducing transcription of p53. Disruption of cellular component, tight junction, assembling related to PKC mutation. As identified, PKCδ correlates with ZO-1, and LOF mutation prevent translocation of ZO-1 to TJ area, leading to errors in TJ assembling, promoting tumor invasion.
© The Authors, published by EDP Sciences, 2021
This is an Open Access article distributed under the terms of the Creative Commons Attribution License 4.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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