scholarly journals XIAP: a potential determinant of ovarian follicular fate

Reproduction ◽  
2012 ◽  
Vol 144 (2) ◽  
pp. 165-176 ◽  
Author(s):  
Hollian R Phillipps ◽  
Peter R Hurst
Keyword(s):  
Granulosa Cells ◽  
Current Knowledge ◽  
Inhibitor Of Apoptosis ◽  
Caspase Inhibitor ◽  
Follicular Atresia ◽  
Inhibitor Of Apoptosis Protein ◽  
Apoptosis Protein ◽  
Potential Determinant

X-linked inhibitor of apoptosis protein (XIAP), a member of the inhibitor of apoptosis protein family, is involved in regulating a number of functions including receptor-mediated intracellular signalling and early development. Its role as an endogenous caspase inhibitor, however, is the most highly characterised. Consequently, this protein has been implicated as an anti-apoptotic factor in the ovary.In vitroandin vivostudies have begun dissecting the stimuli and signalling networks that lead to XIAP upregulation in granulosa cells. The objective of this review is to briefly summarise the current knowledge concerning XIAP and its interactions with different caspases. Furthermore, XIAP's emerging role in the mammalian ovary will be explored and comparison is made with its functions in the mammary gland. Finally, the idea that XIAP may act as a molecular signalling switch in granulosa cells following detachment from underlying layers to promote follicular atresia will be introduced.

Cellular inhibitor of apoptosis protein 2 controls human colonic epithelial restitution, migration, and Rac1 activation

2015 ◽  
Vol 308 (2) ◽  
pp. G92-G99 ◽  
Author(s):  
Jakob Benedict Seidelin ◽  
Sylvester Larsen ◽  
Dorte Linnemann ◽  
Ben Vainer ◽  
Mehmet Coskun ◽  
...  
Keyword(s):  
Wound Healing ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Human Colon ◽  
Inhibitor Of Apoptosis ◽  
Experimental Ulcer ◽  
Inhibitor Of Apoptosis Protein ◽  
Apoptosis Protein

Identification of pathways involved in wound healing is important for understanding the pathogenesis of various intestinal diseases. Cellular inhibitor of apoptosis protein 2 (cIAP2) regulates proliferation and migration in nonepithelial cells and is expressed in human colonocytes. The aim of the study was to investigate the role of cIAP2 for wound healing in the normal human colon. Wound tissue was generated by taking rectosigmoidal biopsies across an experimental ulcer in healthy subjects after 5, 24, and 48 h. In experimental ulcers, the expression of cIAP2 in regenerating intestinal epithelial cells (IECs) was increased at the wound edge after 24 h ( P < 0.05), returned to normal after reepithelialization, and correlated with the inflammatory reaction in the experimental wounds ( P < 0.001). cIAP2 was induced in vitro in regenerating Caco2 IECs after wound infliction ( P < 0.01). Knockdown of cIAP2 caused a substantial impairment of the IEC regeneration through inhibition of migration ( P < 0.005). cIAP2 overexpression lead to formation of migrating IECs and upregulation of expression of RhoA and Rac1 as well as GTP-activation of Rac1. Transforming growth factor-β1 enhanced the expression of cIAP2 but was not upregulated in wounds in vivo and in vitro. NF-κB and MAPK pathways did not affect cIAP2 expression. cIAP2 is in conclusion a regulator of human intestinal wound healing through enhanced migration along with activation of Rac1, and the findings suggest that cIAP2 could be a future therapeutic target to improve intestinal wound healing.

scholarly journals Inhibitor of apoptosis protein expression in glioblastomas and their in vitro and in vivo targeting by SMAC mimetic GDC-0152

2016 ◽  
Vol 7 (8) ◽  
pp. e2325-e2325 ◽  
Author(s):  
A Tchoghandjian ◽  
A Soubéran ◽  
E Tabouret ◽  
C Colin ◽  
E Denicolaï ◽  
...  
Keyword(s):  
Protein Expression ◽  
Inhibitor Of Apoptosis ◽  
Inhibitor Of Apoptosis Protein ◽  
Apoptosis Protein ◽  
Smac Mimetic

Vascular Endothelial Genes That Are Responsive to Tumor Necrosis Factor- In Vitro Are Expressed in Atherosclerotic Lesions, Including Inhibitor of Apoptosis Protein-1, Stannin, and Two Novel Genes

Blood ◽  
1999 ◽  
Vol 93 (10) ◽  
pp. 3418-3431 ◽  
Author(s):  
Anton J.G. Horrevoets ◽  
Ruud D. Fontijn ◽  
Anton Jan van Zonneveld ◽  
Carlie J.M. de Vries ◽  
Jan Wouter ten Cate ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tumor Necrosis ◽  
Inhibitor Of Apoptosis ◽  
Vascular Endothelial ◽  
Inhibitor Of Apoptosis Protein ◽  
Atherosclerotic Lesions ◽  
Apoptosis Protein ◽  
Novel Transcripts ◽  
Necrosis Factor

Activation and dysfunction of endothelial cells play a prominent role in patho-physiological processes such as atherosclerosis. We describe the identification by differential display of 106 cytokine-responsive gene fragments from endothelial cells, activated by monocyte conditioned medium or tumor necrosis factor-. A minority of the fragments (22/106) represent known genes involved in various processes, including leukocyte trafficking, vesicular transport, cell cycle control, apoptosis, and cellular protection against oxidative stress. Full-length cDNA clones were obtained for five novel transcripts that were induced or repressed more than 10-fold in vitro. These novel human cDNAs CA2_1, CG12_1, GG10_2, AG8_1, and GG2_1 encode inhibitor of apoptosis protein-1 (hIAP-1), homologues of apolipoprotein-L, mouse rabkinesin-6, rat stannin, and a novel 188 amino acid protein, respectively. Expression of 4 novel transcripts is shown by in situ hybridization on healthy and atherosclerotic vascular tissue, using monocyte chemotactic protein-1 as a marker for inflammation. CA2_1 (hIAP-1) and AG8_1 are expressed by endothelial cells and macrophage foam cells of the inflamed vascular wall. CG12_1 (apolipoprotein-L like) was specifically expressed in endothelial cells lining the normal and atherosclerotic iliac artery and aorta. These results substantiate the complex change in the gene expression pattern of vascular endothelial cells, which accompanies the inflammatory reaction of atherosclerotic lesions.

scholarly journals The Drosophila Inhibitor of Apoptosis Protein DIAP2 Functions in Innate Immunity and Is Essential To Resist Gram-Negative Bacterial Infection

2006 ◽  
Vol 26 (21) ◽  
pp. 7821-7831 ◽  
Author(s):  
François Leulier ◽  
Nouara Lhocine ◽  
Bruno Lemaitre ◽  
Pascal Meier
Keyword(s):  
Immune Response ◽  
Bacterial Infection ◽  
Null Alleles ◽  
Signaling Cascade ◽  
Inhibitor Of Apoptosis ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Inhibitor Of Apoptosis Protein ◽  
Apoptosis Protein

ABSTRACT The founding member of the inhibitor of apoptosis protein (IAP) family was originally identified as a cell death inhibitor. However, recent evidence suggests that IAPs are multifunctional signaling devices that influence diverse biological processes. To investigate the in vivo function of Drosophila melanogaster IAP2, we have generated diap2 null alleles. diap2 mutant animals develop normally and are fully viable, suggesting that diap2 is dispensable for proper development. However, these animals were acutely sensitive to infection by gram-negative bacteria. In Drosophila, infection by gram-negative bacteria triggers the innate immune response by activating the immune deficiency (imd) signaling cascade, a NF-κB-dependent pathway that shares striking similarities with the pathway of mammalian tumor necrosis factor receptor 1 (TNFR1). diap2 mutant flies failed to activate NF-κB-mediated expression of antibacterial peptide genes and, consequently, rapidly succumbed to bacterial infection. Our genetic epistasis analysis places diap2 downstream of or in parallel to imd, Dredd, Tak1, and Relish. Therefore, DIAP2 functions in the host immune response to gram-negative bacteria. In contrast, we find that the Drosophila TNFR-associated factor (Traf) family member Traf2 is dispensable in resistance to gram-negative bacterial infection. Taken together, our genetic data identify DIAP2 as an essential component of the Imd signaling cascade, protecting the organism from infiltrating microbes.

scholarly journals X-linked inhibitor of apoptosis protein and active caspase-3 expression patterns in antral follicles in the sheep ovary

Reproduction ◽  
2011 ◽  
Vol 142 (6) ◽  
pp. 855-867 ◽  
Author(s):  
Hollian R Phillipps ◽  
Ilona C Kokay ◽  
David R Grattan ◽  
Peter R Hurst
Keyword(s):  
Mrna Expression ◽  
Caspase 3 ◽  
Expression Patterns ◽  
Inhibitor Of Apoptosis ◽  
Mrna Levels ◽  
Follicular Atresia ◽  
Inhibitor Of Apoptosis Protein ◽  
Antral Follicles ◽  
Apoptosis Protein ◽  
Active Caspase

X-linked inhibitor of apoptosis protein (XIAP) interacts with caspases to inhibit their activity, thereby providing a potential mechanism for regulation of granulosa cell apoptosis occurring during follicular atresia. The aim of this study was to determine the presence and localization of XIAP mRNA and protein content in the sheep ovary and compare these expression patterns with active caspase-3 protein in the same antral follicles. Romney ewe estrous cycles (n=25) were synchronized with 2–3 Estrumate injections and ovarian tissue collected during the luteal and follicular phases of the cycle. The presence ofXIAPmRNA was confirmed by RT-PCR using laser capture microdissected ovarian cell samples.XIAPmRNA was subsequently localized byin situhybridization histochemistry and XIAP and active caspase-3 protein visualized by immunohistochemistry. In antral follicles extensive XIAP localization was evident in both granulosa and thecal cells. In contrast, mRNA expression was widespread in granulosa cells and only detected in thecal tissue from a small proportion of antral follicles. Active caspase-3 and XIAP comparative expression analysis showed positiveXIAPmRNA expression in all late luteal phase (day 14) follicles, despite varying levels of active caspase-3 protein. A proportion of follicular phase (days 15 and 16) follicles, however, showed an inverse expression relationship at the protein and mRNA levels in both granulosa and thecal tissue, as did XIAP protein in day 14 follicles. These results suggest high XIAP may prevent activation of caspase-3, thereby regulating follicular atresia in antral follicles and could potentially be utilized as a marker of follicular health.

scholarly journals Molecular Cloning of ILP-2, a Novel Member of the Inhibitor of Apoptosis Protein Family

2001 ◽  
Vol 21 (13) ◽  
pp. 4292-4301 ◽  
Author(s):  
Bettina W. M. Richter ◽  
Samy S. Mir ◽  
Lisa J. Eiben ◽  
Jennifer Lewis ◽  
Stephanie Birkey Reffey ◽  
...  
Keyword(s):  
Molecular Cloning ◽  
Inhibitor Of Apoptosis ◽  
Physical Interaction ◽  
Caspase 9 ◽  
Inhibitor Of Apoptosis Protein ◽  
Normal Tissues ◽  
Apoptosis Protein ◽  
Processed Form

ABSTRACT Inhibitor of apoptosis protein (IAP)-like protein-1 (ILP-1) (also known as X-linked IAP [XIAP] and mammalian IAP homolog A [MIHA]) is a potent inhibitor of apoptosis and exerts its effects, at least in part, by the direct association with and inhibition of specific caspases. Here, we describe the molecular cloning and characterization of a human gene related to ILP-1, termed ILP-2. Despite high homology to ILP-1, ILP-2 is encoded by a distinct gene, which in normal tissues is expressed solely in testis. In contrast to ILP-1, overexpression of ILP-2 had no protective effect on apoptosis mediated by Fas (also known as CD95) or tumor necrosis factor. However, ILP-2 potently inhibited apoptosis induced by overexpression of Bax or by coexpression of caspase 9 with Apaf-1, and preincubation of cytosolic extracts with ILP-2 abrogated caspase activation in vitro. A processed form of caspase 9 could be coprecipitated with ILP-2 from cells, suggesting a physical interaction between ILP-2 and caspase 9. Thus, ILP-2 is a novel IAP family member with restricted specificity for caspase 9.

scholarly journals Essential Role of Survivin, an Inhibitor of Apoptosis Protein, in T Cell Development, Maturation, and Homeostasis

2003 ◽  
Vol 199 (1) ◽  
pp. 69-80 ◽  
Author(s):  
Zheng Xing ◽  
Edward M. Conway ◽  
Chulho Kang ◽  
Astar Winoto
Keyword(s):  
T Cells ◽  
T Cell ◽  
Developmental Stages ◽  
T Cell Development ◽  
Cell Development ◽  
Inhibitor Of Apoptosis ◽  
Proliferating Cells ◽  
Inhibitor Of Apoptosis Protein ◽  
Apoptosis Protein

Survivin is an inhibitor of apoptosis protein that also functions during mitosis. It is expressed in all common tumors and tissues with proliferating cells, including thymus. To examine its role in apoptosis and proliferation, we generated two T cell–specific survivin-deficient mouse lines with deletion occurring at different developmental stages. Analysis of early deleting survivin mice showed arrest at the pre–T cell receptor proliferating checkpoint. Loss of survivin at a later stage resulted in normal thymic development, but peripheral T cells were immature and significantly reduced in number. In contrast to in vitro studies, loss of survivin does not lead to increased apoptosis. However, newborn thymocyte homeostatic and mitogen-induced proliferation of survivin-deficient T cells were greatly impaired. These data suggest that survivin is not essential for T cell apoptosis but is crucial for T cell maturation and proliferation, and survivin-mediated homeostatic expansion is an important physiological process of T cell development.

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