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Evaluation of the role of p53 tumor suppressor post-translational modifications and TTC5 cofactor in lung cancer

Alhebshi, Hasen and Tian, Kun and Patnaik, Lipsita and Taylor, Rebecca and Bezecny, Pavel and Hall, Callum and Muller, Patricia AJ and Safari, Nazila and Menendez Creamer, Delta Patricia and Demonacos, Constantinos and Mutti, Luciano and Bittar, Mohamad Nidal and Krstic-Demonacos, Marija (2021) 'Evaluation of the role of p53 tumor suppressor post-translational modifications and TTC5 cofactor in lung cancer.', International Journal of Molecular Sciences, 22 (24). p. 13198.

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
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Available under License - Creative Commons Attribution 4.0.
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Status:Peer-reviewed
Publisher Web site:https://doi.org/10.3390/ijms222413198
Publisher statement:© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).
Date accepted:02 December 2021
Date deposited:16 December 2021
Date of first online publication:07 December 2021
Date first made open access:16 December 2021

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