Evaluation of the role of p53 tumour suppressor posttranslational modifications and TTC5 cofactor in lung cancer

Alhebshi, H, Tian, K ORCID: https://orcid.org/0000-0001-6170-7382, Patnaik, L, Taylor, R ORCID: https://orcid.org/0000-0001-6699-3867, Bezecny, P, Hall, C, Muller, PAJ, Safari, N, Menendez Creamer, DP, Demonacos, C ORCID: https://orcid.org/0000-0002-4515-755X, Mutti, L ORCID: https://orcid.org/0000-0002-1578-2637, Bittar, MN and Krstic- Demonacos, M ORCID: https://orcid.org/0000-0002-3914-4488 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.

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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.

Item Type: Article
Contributors: Platt, JL (Editor)
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
Schools: Schools > School of Computing, Science and Engineering
Journal or Publication Title: International Journal of Molecular Sciences
Publisher: MDPI
ISSN: 1422-0067
Related URLs:
Funders: Rosemere Cancer Foundation, Libyan Government
SWORD Depositor: Publications Router
Depositing User: Publications Router
Date Deposited: 10 Dec 2021 08:46
Last Modified: 15 Feb 2022 16:58
URI: http://usir.salford.ac.uk/id/eprint/62515

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