Cyclin-dependent kinase inhibitors

Abstract

Stanični ciklus je jedan od najvažnijih procesa koji se događa u stanicama. Omogućuje prenošenje identičnog genetičkog materijala iz generacije u generaciju i osigurava da isti ostane kompletno očuvan. Ciklus je višestruko reguliran različitim signalima i odgovarajućim signalnim putevima. U slučaju nedostatka ili poremećaja regulacije staničnog ciklusa može doći do nekontrolirane proliferacije, oštećenja genoma i na koncu pojave tumora. U ovom radu predstavljene su osnove staničnog ciklusa, kao i mehanizmi koji ga reguliraju. Poseban je osvrt na inhibiciju stanične proliferacije uz pomoć specifičnih proteina inhibitora kinaza ovisnih o ciklinu. Prikazana je struktura, funkcija, mehanička uloga svakog od inhibitora kinaza ovisnih o ciklinu i njegov efektorni put. Gubitak funkcije CDKI zbog pojave različitih oštećenja, mutacija ili epigenetskih promjena ima katastrofalne posljedice na stanicu, pa i čitav organizam. Inhibitori CDK imaju ulogu i u procesu starenja. p21 i p16 imaju sposobnost ireverzibilnog zaustavljanja ciklusa kod starih stanica. Inhibitori kinaza ovisnih o ciklinu važan su obrambeni čimbenik stanica u borbi protiv oštećenja izazvanog bilo raznim agensima, kemijskim i fizičkim, bilo spontano nastalih u stanici, kao i mehanizam zaštite od prokarcinogenih posljedica oštećenih i skraćenih telomera.The cell cycle is one of the most important processes in the cell. It enables the transfer of identical genetic material between generations and assures its complete preservation. The cycle is regulated by multiple signals and corresponding signaling pathways. Defect or lack of the cell cycle regulators could lead to uncontrolled proliferation and genome damage, resulting in carcinogenic processes. In this paper the basics of the cell cycle is presented, as well as the mechanisms that regulates it. The main topic is the cell proliferation inhibition and specific protein cyclin dependent kinase inhibitors. It shows structure, function and mechanical role of each of the cyclin dependent kinases inhibitors, as well as their effectors pathway. DNA damage, mutation or epigenetic alteration could lead to loss of CDKI functions and could have catastrophic consequences on the cell and the entire organism. CDK inhibitors are also involved in a number of other cell mechanisms. p21 and p16 are the main factors of the irreversible cell cycle arrest in senescence. CDKI are an important cell defense response in the fight against damage caused by various chemical and physical agents, or spontaneous arisen in the cell, as well as a defense mechanism against procarcinogenic effects of shortened and damaged telomeres