Descriptive and functional definition of nucleolus – a pathway to cancer therapy

Abstract

Sažetak. Očekuje se da moderna terapija tumora djeluje ciljano i sveobuhvatno. U novim kliničkim ispitivanjima terapije raka primjenjuju se mali molekularni inhibitori transkripcije ribosomalnih gena i aktivatori apoptoze. Model terapije prikazan ovdje je aktivacija supresora tumora koji djeluju u domeni jezgrice. Stanice tumora pokazuju poremećaj regulacije proteina i mutaciju P53 gena koji suprimira rast. Razvoj bolesti definira terapiju. Moderna se definicija bolesti temelji na etiopatogenezi staničnog stresa u kojem sudjeluju brojne organele, uključujući jezgricu. Jezgra i jezgrica su mikroskopski oblici. Ovaj prikaz daje sažet opis onoga što se vidi kada se kaže "jezgrica". Nadalje su opisani kiseli nehistonski proteini koji se okupljaju oko transkripcijskog ustroja RNK polimeraze I te je istaknut značaj njihove vizualizacije za promjenu definicije jezgrice. Osim što je tjelešce u nukleoplazmi i subnuklearna organela, jezgrica se može vizualizirati pomoću njezinih funkcionalnih struktura -AgNOR-a. AgNOR proteini imaju ulogu u nukleolarnom stresu. Svrha ovoga teksta je raspraviti nukleolarni stres.Ključne riječi: biološki stres; bolest; karcinogeneza; stanična jezgrica; terapija Abstract. Modern tumour therapy should be target specific and comprehensive. Recent clinical trials test small molecular inhibitors of transcription of ribosomal genes and activators of apoptosis. We treatise on models of activation of the suppressors of tumour growth acting in the nucleolar domain. Tumour cells demonstrate a disordered protein regulation and mutation of P53 gene which codes for a suppressor of growth. Therapy is guided by pathogenesis. Modern disease definition is based on etiopathogenesis of cell stress, wherein participate numerous organelles, including the nucleolus. Nucleus and nucleolus are forms seen on light microscopy. This presentation focuses on the description of the visible correlate of the notion of "nucleolus". Further to this, acid non-histone proteins which gather around the transcriptional machinery of RNA polymerase I are described, and the significance of their visualisation towards the alteration of the definition of nucleolus is pointed out. Besides being a particle within the nucleoplasm and a subnuclear organelle, the nucleolus is visualized through its functional structures -the AgNORs. The AgNOR proteins have a role in nucleolar stress. The aim of this article is to discuss the nucleolar stress.