Endogenous p53 inhibitor TIRR dissociates systemic metabolic health from oncogenic activity

• Published in: Cell reports (Cambridge) Vol. 43; no. 6; p. 114337
• Main Authors: Tsaousidou, Eva, Chrzanowski, Jędrzej, Drané, Pascal, Lee, Grace Y., Bahour, Nadine, Wang, Zeqiu Branden, Deng, Shijun, Cao, Zhe, Huang, Kaimeng, He, Yizhou, Kaminski, Mateusz, Michalek, Dominika, Güney, Ekin, Parmar, Kalindi, Fendler, Wojciech, Chowdhury, Dipanjan, Hotamışlıgil, Gökhan S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 25.06.2024; Elsevier
• Subjects: Adipose Tissue - metabolism; Animals; cancer metabolism; cancer mouse model of p53 activation; cancer protection; Carcinogenesis - metabolism; Carcinogenesis - pathology; CP: Cancer; CP: Metabolism; Glucose - metabolism; Humans; in vivo physiology in cancer; Insulin Resistance; Male; mevalonate pathway suppression; Mice; Mice, Inbred C57BL; Mice, Knockout; obesity and cancer; overweight and cancer; p53 activation; p53 derepression; p53 inhibitor; RNA-Binding Proteins - metabolism; Tumor Suppressor Protein p53 - metabolism; type 2 diabetes and cancer; obesity and cancer; cancer protection; type 2 diabetes and cancer; p53 derepression; p53 activation; CP: Metabolism; overweight and cancer; mevalonate pathway suppression; cancer mouse model of p53 activation; p53 inhibitor; in vivo physiology in cancer; cancer metabolism; CP: Cancer

It is unclear whether metabolic health corresponds to reduced oncogenesis or vice versa. We study Tudor-interacting repair regulator (TIRR), an inhibitor of p53 binding protein 1 (53BP1)-mediated p53 activation, and the physiological consequences of enhancing tumor suppressor activity. Deleting TIRR...