Role molekulárních chaperonů a ko-chaperonů v biologii nádorů

Molekulární chaperony (heat-shock proteiny, Hsps) jsou proteiny, které udržují intracelulární homeostázu skládáním a stabilizací konformace jiných proteinů. Díky schopnosti chránit proteom před špatně složenými a agregovanými proteiny jsou chaperony nezbytné pro přežití buněk vystavených stresu. Kromě základní funkce v udržování buněčné homeostázy a ochraně před vnějšími stresovými faktory hrají některé molekulární chaperony důležitou roli i při transformaci nádorové buňky. Zvýšená hladina chaperonů byla detekována u mnoha solidních nádorů a hematopoetických malignit. Nárůst aktivity chaperonů v nádorových buňkách odráží jejich schopnost kompenzovat stresové podmínky způsobené hypoxií, zvýšenou proteosyntézou a přítomností mutantních a potenciálně nestabilních proteinů. Chaperony navíc umožňují nádorovým buňkám tolerovat genetické změny stabilizováním terciární struktury mutantních proteinů – typicky onkoproteinů –, které by jinak byly pro buňku letální. Z tohoto pohledu chaperony zprostředkovávají fenotypové vyjádření onkogeních mutací a přispívají k získání všech základních znaků nádorové buňky. Kvůli jejich nezbytné funkci v nádorech ovlivňující současně několik esenciálních onkogenních drah se chaperony staly atraktivním cílem nádorové terapie.

Klíčova slova:
molekulární chaperony – ko-chaperony – Hsp90 – nádorové onemocnění

Autoři: M. Ďurech; B. Vojtesek; P. Müller
Působiště autorů: Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic
Vyšlo v časopise: Klin Onkol 2012; 25(Supplementum 2): 45-49

Práce byla podpořena granty IGA MZ ČR NT/13794-4/2012, GAČR P206/12/G151 a 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: 11. 10. 2012
Přijato: 24. 10. 2012

Souhrn

Klíčova slova:
molekulární chaperony – ko-chaperony – Hsp90 – nádorové onemocnění

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