H Alhebshi
Evaluation of the role of p53 tumour suppressor posttranslational modifications and TTC5 cofactor in lung cancer
Alhebshi, H; Tian, K; Patnaik, L; Taylor, R; Bezecny, P; Hall, C; Muller, PAJ; Safari, N; Menendez Creamer, DP; Demonacos, C; Mutti, L; Bittar, MN; Krstic- Demonacos, M
Authors
K Tian
L Patnaik
R Taylor
P Bezecny
C Hall
PAJ Muller
N Safari
DP Menendez Creamer
C Demonacos
L Mutti
MN Bittar
Prof Marija Krstic-Demonacos M.Krstic-Demonacos@salford.ac.uk
Professor of Molecular Medicine
Contributors
JL Platt
Editor
Abstract
Mutations in the p53 tumor suppressor are found in over 50% of cancers. p53 function is controlled through posttranslational modifications and cofactor interactions. In this study, we investigated the posttranslationally modified p53, including p53 acetylated at lysine 382 (K382), p53 phosphorylated at serine 46 (S46), and the p53 cofactor TTC5/STRAP (Tetratricopeptide repeat domain 5/ Stress-responsive activator of p300-TTC5) proteins in lung cancer. Immunohistochemical (IHC) analysis of lung cancer tissues from 250 patients was carried out and the results were correlated with clinicopathological features. Significant associations between total or modified p53 with a higher grade of the tumour and shorter overall survival (OS) probability were detected, suggesting that mutant and/or modified p53 acts as an oncoprotein in these patients. Acetylated at K382 p53 was predominantly nuclear in some samples and cytoplasmic in others. The localization of the K382 acetylated p53 was significantly associated with the gender and grade of the disease. The TTC5 protein levels were significantly associated with the grade, tumor size, and node involvement in a complex manner. SIRT1 expression was evaluated in 50 lung cancer patients and significant positive correlation was found with p53 S46 intensity, whereas negative TTC5 staining was associated with SIRT1 expression. Furthermore, p53 protein levels showed positive association with poor OS, whereas TTC5 protein levels showed positive association with better OS outcome. Overall, our results indicate that an analysis of p53 modified versions together with TTC5 expression, upon testing on a larger sample size of patients, could serve as useful prognostic factors or drug targets for lung cancer treatment.
Citation
Alhebshi, H., Tian, K., Patnaik, L., Taylor, R., Bezecny, P., Hall, C., …Krstic- Demonacos, M. (2021). Evaluation of the role of p53 tumour suppressor posttranslational modifications and TTC5 cofactor in lung cancer. International Journal of Molecular Sciences, 22(24), e13198. https://doi.org/10.3390/ijms222413198
Journal Article Type | Article |
---|---|
Acceptance Date | Dec 2, 2021 |
Publication Date | Dec 7, 2021 |
Deposit Date | Dec 10, 2021 |
Publicly Available Date | Dec 10, 2021 |
Journal | International Journal of Molecular Sciences |
Print ISSN | 1661-6596 |
Publisher | MDPI |
Volume | 22 |
Issue | 24 |
Pages | e13198 |
DOI | https://doi.org/10.3390/ijms222413198 |
Publisher URL | https://doi.org/10.3390/ijms222413198 |
Related Public URLs | https://www.mdpi.com/journal/ijms |
Additional Information | Additional Information : ** From MDPI via Jisc Publications Router ** Licence for this article: https://creativecommons.org/licenses/by/4.0/ **Journal IDs: eissn 1422-0067 **History: published 07-12-2021; accepted 02-12-2021 Funders : Rosemere Cancer Foundation;Libyan Government |
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Licence
http://creativecommons.org/licenses/by/4.0/
Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/
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