Apoptosis Regulation by Inhibitors of Programmed Cell Death

Abstract

Summary: Apoptosis is a form of cell death which is important in many physiological processes. Four apoptotic mechanisms have been identified but two have been well examined: the intrinsic and the extrinsic mechanism. Due to many pro/antiapoptotic factors, these processes take place on a physiologically useful level. In cases of apoptosis dysregu lation, illnesses occur such as neurodegenerative diseases combined with an increased level of cell death or cancerogenesis associated with uncontrolled cell proliferation. Apoptosis can be triggered by the activation of the first caspase in a series and stopped by its deactivation, which represents a new challenge: determining the »point of no return«. Besides the antiapoptotic proteins (Bcl 2, Bcl XL), a family of proteins called the Inhibitors of Apoptosis Proteins (IAPs) play a key role in the regulation of apoptosis. Members of the IAP family are: cIAP1, cIAP2, XIAP, Survivin, Livin and TsIAP. Domain BIR is the most important in the IAP structure since it determines their specificity for caspases. The interaction of IAPs with caspases is complex and not completely understood, however, IAPs are considered to be important target proteins in the therapy of tumor and autoimmune diseases. Keywords: IAP protein (apoptosis), caspases, programmed cell death type IKratak sadr`aj: Apoptoza predstavlja oblik }elijske smrti i va`na je u mnogim fiziolo{kim procesima. Postojẽ etiri oblika }elijske smrti a dva su dobro prou~ena: unutra{nji i spolja{nji. Zahvaljuju}i mnogim pro/antiapoptoti~kim faktorima, ovaj proces se odvija na fiziolo{ki korisnom nivou. U slu~aju disregulacije apoptoze nastaju bolesti kao {to su neurodegenerativna oboljenja udru`ena sa povi{enim nivoom }elijske smrti ili karcinogeneza udru`ena sa nekontrolisanom }elijskom proliferacijom. Apoptozu mo`e po krenuti aktivacija prve kaspaze u nizu i prekinuti njena deaktivacija, {to predstavlja novi izazov: odrediti »ta~ku bez povratka«. Pored antiapoptoti~nih proteina (Bcl 2, Bcl XL), familija proteina nazvanih inhibitori apoptoze (eng. Inhibitors of Apoptosis Proteins, IAPs) igra klju~nu ulogu u procesu regulacije. Pripadnici familije IAP su: cIAP1, cIAP2, XIAP, survivin, livin i TsIAP. Domen BIR je naj zna~ajniji u strukturi IAP budu}i da odre|uje specifi~nost ka kaspazama. Interakcija IAP sa kaspazama je kompleksna i nedovoljno istra`ena, me|utim, smatra se da IAPs pred stavljaju va`ne ciljne proteine u terapiji tumora i auto imunih oboljenja.

Dual silencing of Bcl-2 and Survivin by HSV-1 vector shows better antitumor efficacy in higher PKR phosphorylation tumor cells in vitro and in vivo

“…8 Therefore, the antitumor activity 7,[36][37][38][39] RNAi therapy was another choice to inhibit overexpression of oncogenes that contribute to the escape of tumor cells from apoptosis. 22,40 There are two apoptosis pathways, intrinsic pathway and extrinsic pathway, in mammalian cells. 36 These pathways can be distinguished by whether these require Bcl-2 family proteins or caspases are crucial for their execution.…”

Brain Injury Alters Ectonucleotidase Activities and Adenine Nucleotide Levels in Rat Serum / Povreda Mozga Menja Ektonukleotidazne Aktivnosti I Nivo Adeninskih Nukleotida U Serumu Pacova

“…Since ATP acts as a ligand at multiple P2 receptors, alterations in its serum concentration after the injury may affect numerous cellular functions. For instance, at high micromolar concentrations, ATP promotes vasodilatation ( 4 ) and triggers proinflammatory effector functions ( 4 , 44 ) including production of proinflammatory cytokines ( 45 – 47 ).…”