Mechanisms of tumor suppressor gene TP53 inactivation in tumor development

Tumori su nakupine promijenjenih stanica koje nekontrolirano rastu i dijele se, a uklanjanjem uzroka njihove pojave njihovo dijeljenje ne prestaje. U kancerogenezi, skupina gena koja ima bitno značenje su tumor supresorski geni. Jedan od njih je gen TP53 koji kodira za nuklearni fosfoprotein p53 i ima ulogu u regulaciji staničnog ciklusa, apoptozi i staničnom starenju. U normalnim uvjetima TP53 inhibira proliferaciju stanica i nekontrolirano dijeljenje, no pojavom mutacija dolazi do inhibicije njegovog supresorskog djelovanja te to pridonosi pojavi tumora. U ovom radu, naglasak je stavljan na somatske i germinativne mutacije koje utječu na ekspresiju p53, polimorfizme p53 te interakcije s drugim koefektorima poput MDM2 i KAP1 te mikroRNA molekula. Također, naveden je pregled humanih tumora koji sadrže mutacije tumor supresorskog gena TP53 redom prema učestalosti pojave u populaciji.Tumors are masses of tissue that grow abnormally and by removing the cause of their occurrence, their growth does not stop. In cancerogenesis, a group of genes that are of crucial importance are tumor suppressor genes. One of them is the TP53 gene that codes for nuclear phosphoprotein p53 and plays a role in regulating cell cycle, apoptosis and cellular ageing. Under normal conditions, TP53 inhibits cell proliferation and uncontrollable growth, but when mutations occur, it results in inhibition of its suppressor activity and this contributes to the tumor development. In this paper, emphasis is placed on somatic and germinative mutations affecting expression of p53, polymorphisms of p53 and interaction with other coefficients such as MDM2 and KAP1 and microRNA molecules. Also, a review of human tumors containing tumor suppressor TP53 tumor mutations is reported according to the frequency of occurrence in the population