Evaluation of the Role of p53 Tumour Suppressor Posttranslational Modifications and TTC5 Cofactor in Lung Cancer
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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/24/13198 |
| _version_ | 1797503975523614720 |
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| author | Hasen Alhebshi Kun Tian Lipsita Patnaik Rebecca Taylor Pavel Bezecny Callum Hall Patricia Anthonia Johanna Muller Nazila Safari Delta Patricia Menendez Creamer Constantinos Demonacos Luciano Mutti Mohamad Nidal Bittar Marija Krstic-Demonacos |
| author_facet | Hasen Alhebshi Kun Tian Lipsita Patnaik Rebecca Taylor Pavel Bezecny Callum Hall Patricia Anthonia Johanna Muller Nazila Safari Delta Patricia Menendez Creamer Constantinos Demonacos Luciano Mutti Mohamad Nidal Bittar Marija Krstic-Demonacos |
| author_sort | Hasen Alhebshi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T03:58:03Z |
| format | Article |
| id | doaj.art-f45764dd75bd4a69b6b080b5d91eca3b |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:58:03Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f45764dd75bd4a69b6b080b5d91eca3b2023-11-23T08:42:41ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-12-0122241319810.3390/ijms222413198Evaluation of the Role of p53 Tumour Suppressor Posttranslational Modifications and TTC5 Cofactor in Lung CancerHasen Alhebshi0Kun Tian1Lipsita Patnaik2Rebecca Taylor3Pavel Bezecny4Callum Hall5Patricia Anthonia Johanna Muller6Nazila Safari7Delta Patricia Menendez Creamer8Constantinos Demonacos9Luciano Mutti10Mohamad Nidal Bittar11Marija Krstic-Demonacos12School of Science, Engineering and Environment, University of Salford, Cockcroft Building 305, Manchester M5 4WT, UKInstitute of Biological Anthropology, School of Basical Medical Science, Jinzhou Medical University, Jinzhou 121001, ChinaBlackpool Teaching Hospitals NHS Foundation Trust, Blackpool FY3 8NR, UKBlackpool Teaching Hospitals NHS Foundation Trust, Blackpool FY3 8NR, UKBlackpool Teaching Hospitals NHS Foundation Trust, Blackpool FY3 8NR, UKCancer Research UK Manchester Institute, The University of Manchester, Alderley Park, Manchester SK10 4TG, UKCancer Research UK Manchester Institute, The University of Manchester, Alderley Park, Manchester SK10 4TG, UKSchool of Science, Engineering and Environment, University of Salford, Cockcroft Building 305, Manchester M5 4WT, UKSchool of Science, Engineering and Environment, University of Salford, Cockcroft Building 305, Manchester M5 4WT, UKDivision of Pharmacy and Optometry, Faculty of Biology, Medicine and Health, School of Health Sciences, The University of Manchester, Stopford Building, 3.124 Oxford Road, Manchester M13 9PT, UKCenter for Biotechnology, Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, Philadelphia, PA 19122, USABlackpool Teaching Hospitals NHS Foundation Trust, Blackpool FY3 8NR, UKSchool of Science, Engineering and Environment, University of Salford, Cockcroft Building 305, Manchester M5 4WT, UKMutations 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.https://www.mdpi.com/1422-0067/22/24/13198p53TTC5lung cancer |
| spellingShingle | Hasen Alhebshi Kun Tian Lipsita Patnaik Rebecca Taylor Pavel Bezecny Callum Hall Patricia Anthonia Johanna Muller Nazila Safari Delta Patricia Menendez Creamer Constantinos Demonacos Luciano Mutti Mohamad Nidal Bittar Marija Krstic-Demonacos Evaluation of the Role of p53 Tumour Suppressor Posttranslational Modifications and TTC5 Cofactor in Lung Cancer International Journal of Molecular Sciences p53 TTC5 lung cancer |
| title | Evaluation of the Role of p53 Tumour Suppressor Posttranslational Modifications and TTC5 Cofactor in Lung Cancer |
| title_full | Evaluation of the Role of p53 Tumour Suppressor Posttranslational Modifications and TTC5 Cofactor in Lung Cancer |
| title_fullStr | Evaluation of the Role of p53 Tumour Suppressor Posttranslational Modifications and TTC5 Cofactor in Lung Cancer |
| title_full_unstemmed | Evaluation of the Role of p53 Tumour Suppressor Posttranslational Modifications and TTC5 Cofactor in Lung Cancer |
| title_short | Evaluation of the Role of p53 Tumour Suppressor Posttranslational Modifications and TTC5 Cofactor in Lung Cancer |
| title_sort | evaluation of the role of p53 tumour suppressor posttranslational modifications and ttc5 cofactor in lung cancer |
| topic | p53 TTC5 lung cancer |
| url | https://www.mdpi.com/1422-0067/22/24/13198 |
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