Evolution and Structure of API5 and Its Roles in Anti-apoptosis

2020 ◽  
Vol 27 ◽  
Author(s):  
Meishan Chen ◽  
Weiwei Wu ◽  
Dongwu Liu ◽  
Yanhua Lv ◽  
Hongkuan Den ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Responses ◽  
Physiological Mechanism ◽  
The Other ◽  
Effective Inhibitor ◽  
Inhibitors Of Apoptosis ◽  
Inhibitors Of Apoptosis Proteins ◽  
Apoptosis Inhibitor ◽  
Apoptosis Proteins

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.

scholarly journals Apoptosis Regulation by Inhibitors of Programmed Cell Death

2013 ◽  
Vol 32 (3) ◽  
pp. 207-213 ◽  
Author(s):  
Danica Marković ◽  
Vidosava Đorđević
Keyword(s):  
Cell Death ◽  
Inhibitors Of Apoptosis ◽  
Antiapoptotic Proteins ◽  
Physiological Processes ◽  
Important Target ◽  
Point Of No Return ◽  
Inhibitors Of Apoptosis Proteins ◽  
Apoptosis Regulation ◽  
Apoptosis Proteins ◽  
Uncontrolled Cell Proliferation

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.

Inhibitors of apoptosis proteins (IAPs) are required for effective T-cell expansion/survival during antiviral immunity in mice

Blood ◽  
2014 ◽  
Vol 123 (5) ◽  
pp. 659-668 ◽  
Author(s):  
Ian E. Gentle ◽  
Isabel Moelter ◽  
Nadja Lechler ◽  
Sarah Bambach ◽  
Smiljka Vucikuja ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Cell Expansion ◽  
Tumor Necrosis ◽  
Activated T Cells ◽  
Inhibitors Of Apoptosis ◽  
Key Points ◽  
Inhibitors Of Apoptosis Proteins ◽  
Apoptosis Proteins ◽  
Necrosis Factor

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.

scholarly journals Characterization of Fortilin, a Novel Antiapoptotic Protein

2001 ◽  
Vol 276 (50) ◽  
pp. 47542-47549 ◽  
Author(s):  
Franklin Li ◽  
Di Zhang ◽  
Ken Fujise
Keyword(s):  
Cell Death ◽  
Hela Cells ◽  
Blot Analysis ◽  
Normal Tissue ◽  
Inhibitors Of Apoptosis ◽  
Antiapoptotic Protein ◽  
Inhibitors Of Apoptosis Proteins ◽  
Apoptosis Proteins ◽  
Mcf 7

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.

scholarly journals The role of B7 family molecules in hematologic malignancy

Blood ◽  
2013 ◽  
Vol 121 (5) ◽  
pp. 734-744 ◽  
Author(s):  
Paul Greaves ◽  
John G. Gribben
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Responses ◽  
Hematologic Malignancy ◽  
Surface Proteins ◽  
Cell Responses ◽  
Inducible Costimulator ◽  
Programmed Cell Death 1 ◽  
B7 Family

AbstractThe B7 family consists of structurally related, cell-surface proteins that regulate immune responses by delivering costimulatory or coinhibitory signals through their ligands. Eight family members have been identified to date including CD80 (B7-1), CD86 (B7-2), CD274 (programmed cell death-1 ligand [PD-L1]), CD273 (programmed cell death-2 ligand [PD-L2]), CD275 (inducible costimulator ligand [ICOS-L]), CD276 (B7-H3), B7-H4, and B7-H6. B7 ligands are expressed on both lymphoid and nonlymphoid tissues. The importance of the B7 family in regulating immune responses is clear from their demonstrated role in the development of immunodeficiency and autoimmune diseases. Manipulation of the signals delivered by B7 ligands shows great potential in the treatment of cancers including leukemias and lymphomas and in regulating allogeneic T-cell responses after stem cell transplantation.

scholarly journals Differentiating life and death: An inflammatory affair

2018 ◽  
Author(s):  
Dustin Lane
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Death ◽  
Cell Differentiation ◽  
Programmed Cell Death ◽  
Signaling Networks ◽  
Inhibitors Of Apoptosis ◽  
Life And Death ◽  
Cell Death Signaling ◽  
Cycle Dependent

Programmed cell death signaling networks are frequently activated to coordinate the process of cell differentiation, and a variety of apoptotic events can mediate the process. This can include the ligation of death receptors, the activation of downstream caspases, and the induction of chromatin fragmentation, and all of these events can occur without downstream induction of death. Importantly, regulators of programmed cell death also have established roles in mediating differentiation. This review will provide an overview of apoptosis and its regulation by Inhibitors of Apoptosis (IAPs) and Bcl-2 family members. It will then outline the cross-talk between NF-ĸB and apoptotic signaling in the regulation of apoptosis before discussing the function of these regulators in the control of cell differentiation. It will end on a discussion of how a DNA damage-directed, cell cycle-dependent differentiation program may be controlled across multiple passages through cell cycle, and will assert that the failure to properly differentiate is the underlying cause of cancer.

Recent Advances on Inhibitors of Apoptosis Proteins (IAP) Particularly with Reference to Patents

2017 ◽  
pp. 271-296
Author(s):  
Riyaz Syed ◽  
Prema L. Mallipeddi ◽  
Syed Mohammed Ali Hussaini ◽  
Rahul V. Patel ◽  
A. Prasanth Saraswati ◽  
...  
Keyword(s):  
Inhibitors Of Apoptosis ◽  
Recent Advances ◽  
Inhibitors Of Apoptosis Proteins ◽  
Apoptosis Proteins

Inhibitors of Apoptosis Proteins

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

Inhibitors of Apoptosis Proteins Expression and Their Prognostic Significance in Colorectal Carcinoma

2011 ◽  
Vol 45 (4) ◽  
pp. 397
Author(s):  
Kyung-Hwa Lee ◽  
Soong Lee ◽  
Hyeon-Min Lee ◽  
Seung-Chul Back ◽  
Sung-Bum Cho ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Prognostic Significance ◽  
Inhibitors Of Apoptosis ◽  
Inhibitors Of Apoptosis Proteins ◽  
Apoptosis Proteins

scholarly journals The Opposing Roles of Cellular Inhibitor of Apoptosis Proteins in Cancer

ISRN Oncology ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
R. Lau ◽  
M. A. C. Pratt
Keyword(s):  
Inhibitor Of Apoptosis ◽  
Inhibitors Of Apoptosis ◽  
Inhibitor Of Apoptosis Protein ◽  
Hematopoietic Malignancies ◽  
Constitutive Activation ◽  
Apoptosis Protein ◽  
Inhibitors Of Apoptosis Proteins ◽  
Cellular Inhibitors ◽  
And Function ◽  
Apoptosis Proteins

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.

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