p53: The Multifaceted Roles of Covalent Modifications in Cancer
Grigoreva T.A. Romanova A.A. Tribulovich V.G. Pestov N.B. Oganov R.A. Kovaleva D.K. Korneenko T.V. Barlev N.A.
December 2024Multidisciplinary Digital Publishing Institute (MDPI)
Pharmaceuticals
2024#17Issue 12
The p53 protein has attracted huge research interest over several decades due to its role as one of the most important tumor suppressors in mammals, which orchestrates a synchronous response from normal cells in the body to various forms of stress. The diverse cellular activities of the p53 protein are regulated mainly via its post-translational modifications (PTMs). PTMs affect p53 on several levels: at the level of the assembly of tetrameric complexes on DNA to transactivate its target genes, at the level of the assembly of tetrameric complexes on DNA to transactivate its target genes; at the level of proteolysis in the absence of stress; and on the contrary, at the level of augmented protein stability in response to stress signals. Disruptions in these regulatory mechanisms can lead to deviations from normal cellular function, boosting tumor initiation and progression. Conversely, targeted interventions in these pathways could prove beneficial for the development of antitumor therapies. Advancing our understanding of p53 modifiers and the proteins involved in its regulation equips researchers with an expanded toolkit for studying cellular processes and for developing biologically active molecules that influence p53-mediated responses.
E3 ubiquitin ligases , p53 , posttranslational modifications
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St. Petersburg State Institute of Technology, St-Petersburg, 190013, Russian Federation
Institute of Biomedical Chemistry, Moscow, 119121, Russian Federation
Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products, Moscow, 108819, Russian Federation
Vavilov Institute of General Genetics, Moscow, 119991, Russian Federation
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, 117997, Russian Federation
Department of Biochemistry, Lomonosov Moscow State University, Moscow, 19991, Russian Federation
Laboratory of Gene Expression Regulation, Institute of Cytology RAS, Saint-Petersburg 194064, Russian Federation
Department of Biomedicine, School of Medicine, Nazarbayev University, Astana, 02000, Kazakhstan
St. Petersburg State Institute of Technology
Institute of Biomedical Chemistry
Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products
Vavilov Institute of General Genetics
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry
Department of Biochemistry
Laboratory of Gene Expression Regulation
Department of Biomedicine
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