Post-translational regulation of the p53 tumor suppressor activity

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Abstract

P53, encoded by the TP53 gene, has attracted researchers’ interest for several decades as a key human tumor suppressor protein. P53-mediated tumor suppression is achieved through transactivation of its target genes, or as a consequence of direct binding of p53 to protein targets that are involved in the regulation of various cellular processes. The review briefly discusses mechanisms involved in the regulation of p53 activity at the protein level – from oligomerization required for the implementation of p53 transactivation mechanisms to ubiquitin-dependent proteolysis that maintains a low level of this proapoptotic protein in normal cells. The main enzymes involved in various post-translational modifications and the effects they can lead to are noted. Rational intervention in these pathways at one stage or another can be relevant both for research purposes and in the applied aspect, particularly for the anti-cancer drug development.

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A. A. Romanova

Saint Petersburg State Institute of Technology

Author for correspondence.
Email: angeliina.romanova@outlook.com
Russian Federation, Saint Petersburg, 190013

T. A. Grigoryeva

Saint Petersburg State Institute of Technology

Email: angeliina.romanova@outlook.com
Russian Federation, Saint Petersburg, 190013

V. G. Tribulovich

Saint Petersburg State Institute of Technology

Email: angeliina.romanova@outlook.com
Russian Federation, Saint Petersburg, 190013

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2. Fig. 1. Functions of p53 in a multicellular organism.

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3. Fig. 2. The main sites of posttranslational modifications shown on the domain structure of full-size p53 (p53a/FLp53). TAD – transactivation domain; PRD – proline–rich domain; DBD - DNA–binding domain; OD – oligomerization domain; CRD - C-terminal regulatory domain.

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