Regulace syntézy p53

English version

Autoři: A. Ponnuswamy ^1,2; R. Fahraeus ²
Působiště autorů: Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic ¹; Cibles Therapeutiques, INSERM Unité 940, Institut de Génétique Moléculaire, Université Paris 7, Paris, France ²
Vyšlo v časopise: Klin Onkol 2012; 25(Supplementum 2): 32-37

Práce byla podpořena Evropským fondem pro regionální rozvoj a státním rozpočtem České republiky (OP VaVpI – RECAMO, CZ.1.05/2.1.00/03.0101).

Autoři deklarují, že v souvislosti s předmětem studie nemají žádné komerční zájmy.

Redakční rada potvrzuje, že rukopis práce splnil ICMJE kritéria pro publikace zasílané do bi omedicínských časopisů.

Obdrženo: 21. 10. 2012
Přijato: 5. 11. 2012

Souhrn

Regulace exprese proteinu p53 je kritická pro kontrolu jeho aktivity v normálních i poškozených buňkách. Velmi dobře je popsána úloha E3 ubikvitin ligázy MDM2, která je za normálních podmínek zodpovědná za degradaci p53 v proteazomu a je esenciální při kontrole aktivity p53 během vývoje organizmu. Nadměrná exprese MDM2 spolu s některými dalšími E3 ligázami podílejícími se rovněž na regulaci stability p53 byla prokázána u řady lidských nádorů, což jen podtrhuje význam posttranslační regulace hladiny proteinu p53. Za stresových podmínek se hladina TP53 na úrovni mRNA zásadně nemění, naopak vše nasvědčuje tomu, že syntéza proteinu p53 je řízena především na úrovni iniciace translace, což představuje významný mechanizmus zodpovědný za kontrolu exprese p53. Na druhou stranu současné práce ukazují, že i TP53 mRNA hraje důležitou roli při regulaci aktivity proteinu p53 v buňce. Proto jsme se v této práci zaměřili a diskutujeme mechanizmy zodpovědné za kontrolu syntézy proteinu p53 a jejich úlohu při regulaci p53 aktivity za normálních podmínek a při různých typech stresu.

Klíčová slova:
syntéza p53 – odpověď na stres – IRES – proteosyntéza – fyziologický stres – RNA-vazebné proteiny

Zdroje

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