scholarly journals Apoptosis Regulation by Inhibitors of Programmed Cell Death

2013 ◽  
Vol 32 (3) ◽  
pp. 207-213 ◽  
Author(s):  
Danica Marković ◽  
Vidosava Đorđević

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.

Blood ◽  
2014 ◽  
Vol 123 (5) ◽  
pp. 659-668 ◽  
Author(s):  
Ian E. Gentle ◽  
Isabel Moelter ◽  
Nadja Lechler ◽  
Sarah Bambach ◽  
Smiljka Vucikuja ◽  
...  

Key Points IAPs are required for survival and expansion of activated T cells. IAP antagonists sensitize to tumor necrosis factor (TNF)-induced cell death of activated T cells during viral infection.


2020 ◽  
Vol 27 ◽  
Author(s):  
Meishan Chen ◽  
Weiwei Wu ◽  
Dongwu Liu ◽  
Yanhua Lv ◽  
Hongkuan Den ◽  
...  

Abstract: Apoptosis, also named programmed cell death, is a highly conserved physiological mechanism. Apoptosis plays crucial roles in many life processes, such as tissue development, organ formation, homeostasis maintenance, resistance against external aggression, and immune responses. Apoptosis is regulated by many genes, among which Apoptosis Inhibitor-5 (API5) is an effective inhibitor, though the structure of API5 is completely different from the other known Inhibitors Of Apoptosis Proteins (IAPs). Due to its high expression in many types of tumors, API5 has received extensive attention, and may be an effective target for cancer treatment. In order to comprehensively and systematically understand the biological roles of API5, we summarized the evolution and structure of API5 and its roles in anti-apoptosis in this review.


2001 ◽  
Vol 276 (50) ◽  
pp. 47542-47549 ◽  
Author(s):  
Franklin Li ◽  
Di Zhang ◽  
Ken Fujise

Apoptosis is meticulously controlled in living organisms. Its dysregulation has been shown to play a key role in a number of human diseases, including neoplastic, cardiovascular, and degenerative disorders. Bcl-2 family member proteins and inhibitors of apoptosis proteins are two major negative regulators of apoptosis. We report here the characterization of novel antiapoptotic protein, fortilin, which we identified through yeast two-hybrid library screening. Sequence analysis of fortilin revealed it to be a 172-amino acid polypeptide highly conserved from mammals to plants. Fortilin is structurally unrelated to either Bcl-2 family member proteins or inhibitors of apoptosis proteins. Northern blot analysis showed the fortilin message to be ubiquitous in normal tissue but especially abundant in the liver, kidney, and small intestine. Western blot analysis using anti-fortilin antibody showed more extensive expression in cancerous cell lines (H1299, MCF-7, and A549) than in cell lines derived from normal tissue (HEK293). Immunocytochemistry using HeLa cells transiently expressing FLAG-tagged fortilin and immunohistochemistry using human breast ductal carcinoma tissue and anti-fortilin antibody both showed that fortilin is predominantly localized in the nucleus. Functionally, the transient overexpression of fortilin in HeLa cells prevented them, in a dose-dependent fashion, from undergoing etoposide-induced apoptosis. Consistently, U2OS cells stably expressing fortilin protected the cells from cell death induced by etoposide over various concentrations and durations of exposure. In addition, fortilin overexpression inhibited caspase-3-like activity as assessed by the cleavage of fluorogenic substrate benzyloxycarbonyl-DEVD-7-amido-4-(trifluoromethyl)coumarin. Furthermore, the antisense depletion of fortilin from breast cancer cell line MCF-7 was associated with massive cell death. These data suggest that fortilin represents a novel antiapoptotic protein involved in cell survival and apoptosis regulation.


Author(s):  
Riyaz Syed ◽  
Prema L. Mallipeddi ◽  
Syed Mohammed Ali Hussaini ◽  
Rahul V. Patel ◽  
A. Prasanth Saraswati ◽  
...  

2003 ◽  
pp. 29-46
Author(s):  
Peter Liston ◽  
Wai Gin Fong ◽  
Robert G. Korneluk

2011 ◽  
Vol 45 (4) ◽  
pp. 397
Author(s):  
Kyung-Hwa Lee ◽  
Soong Lee ◽  
Hyeon-Min Lee ◽  
Seung-Chul Back ◽  
Sung-Bum Cho ◽  
...  

ISRN Oncology ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
R. Lau ◽  
M. A. C. Pratt

Cellular inhibitors of apoptosis proteins 1 and 2 (cIAP1/2) are members of the inhibitor of apoptosis protein (IAP) family that has been implicated in the pathology of human cancers due to their overexpression and function as blockers of cell death in various cancers. As a result, small molecule IAP antagonists have been developed and are currently under clinical evaluation for potential therapeutic use. In contrast, recent evidence has indicated a tumour-suppressing role for the cIAPs. Mutations in or loss of cIAPs have been identified as molecular lesions that contribute to constitutive activation of NF-κB in hematopoietic malignancies. These studies reveal a context-dependent role for the cIAPs wherein both their overexpression and loss may contribute to tumourigenesis.


2019 ◽  
Vol 28 (8) ◽  
pp. 1132-1160 ◽  
Author(s):  
Zabiulla Zabiulla ◽  
Vikas H. Malojirao ◽  
Yasser Hussein Eissa Mohammed ◽  
Prabhu Thirusangu ◽  
B. T. Prabhakar ◽  
...  

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