Search results for "Inhibitor of apoptosis"

Marine Actinomycetes-Derived Secondary Metabolites Overcome TRAIL-Resistance via the Intrinsic Pathway through Downregulation of Survivin and XIAP

2020

Resistance of cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis represents the major hurdle to the clinical use of TRAIL or its derivatives. The discovery and development of lead compounds able to sensitize tumor cells to TRAIL-induced cell death is thus likely to overcome this limitation. We recently reported that marine actinomycetes&rsquo

The Anti-apoptotic Murine Cytomegalovirus Protein vMIA-m38.5 Induces Mast Cell Degranulation.

2020

Mast cells (MC) represent "inbetweeners" of the immune system in that they are part of innate immunity by acting as first-line sentinels for environmental antigens but also provide a link to adaptive immunity by secretion of chemokines that recruit CD8 T cells to organ sites of infection. An interrelationship between MC and cytomegalovirus (CMV) has been a blank area in science until recently when the murine model revealed a role for MC in the resolution of pulmonary infection by murine CMV (mCMV). As to the mechanism, MC were identified as a target cell type of mCMV. Infected MC degranulate and synthesize the CC-chemokine ligand-5 (CCL-5), which is released to attract protective virus-spec…

Peroxisome proliferator-activated receptor-γ coactivator-1α mediates neuroprotection against excitotoxic brain injury in transgenic mice: role of mit…

2016

Peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) is a transcriptional coactivator involved in the regulation of mitochondrial biogenesis and cell defense. The functions of PGC-1α in physiology of brain mitochondria are, however, not fully understood. To address this we have studied wild-type and transgenic mice with a two-fold overexpression of PGC-1α in brain neurons. Data showed that the relative number and basal respiration of brain mitochondria were increased in PGC-1α transgenic mice compared with wild-type mitochondria. These changes occurred concomitantly with altered levels of proteins involved in oxidative phosphorylation (OXPHOS) as studied by proteomi…

How Can Interleukin-1 Receptor Antagonist Modulate Distinct Cell Death Pathways?

2018

Multiple mechanisms of cell death exist (apoptosis, necroptosis, pyroptosis) and the subtle balance of several distinct proteins and inhibitors tightly regulates the cell fate toward one or the other pathway. Here, by combining coimmunoprecipitation, enzyme assays, and molecular simulations, we ascribe a new role, within this entangled regulatory network, to the interleukin-1 receptor antagonist (IL-1Ra). Our study enlightens that IL-1Ra, which usually inhibits the inflammatory effects of IL-1α/β by binding to IL-1 receptor, under advanced pathological states prevents apoptosis and/or necroptosis by noncompetitively inhibiting the activity of caspase-8 and -9. Consensus docking, followed by…

2018

The cellular inhibitor of apoptosis 1 (cIAP1) is an E3-ubiquitin ligase that regulates cell signaling pathways involved in fundamental cellular processes including cell death, cell proliferation, cell differentiation and inflammation. It recruits ubiquitination substrates thanks to the presence of three baculoviral IAP repeat (BIR) domains at its N-terminal extremity. We previously demonstrated that cIAP1 promoted the ubiquitination of the E2 factor 1 (E2F1) transcription factor. Moreover, we showed that cIAP1 was required for E2F1 stabilization during the S phase of cell cycle and in response to DNA damage. Here, we report that E2F1 binds within the cIAP1 BIR3 domain. The BIR3 contains a s…

2020

Over the last decade, the E3-ubiquitine ligases from IAP (Inhibitor of Apoptosis) family have emerged as potent regulators of immune response. In immune cells, they control signaling pathways driving differentiation and inflammation in response to stimulation of tumor necrosis factor receptor (TNFR) family, pattern-recognition receptors (PRRs), and some cytokine receptors. They are able to control the activity, the cellular fate, or the stability of actors of signaling pathways, acting at different levels from components of receptor-associated multiprotein complexes to signaling effectors and transcription factors, as well as cytoskeleton regulators. Much less is known about ubiquitination …

SMAC mimetics promote NIK-dependent inhibition of CD4 + T H 17 cell differentiation

2019

Second mitochondria-derived activator of caspase (SMAC) mimetics (SMs) are selective antagonists of the inhibitor of apoptosis proteins (IAPs), which activate noncanonical NF-κB signaling and promote tumor cell death. Through gene expression analysis, we found that treatment of CD4+ T cells with SMs during T helper 17 (TH17) cell differentiation disrupted the balance between two antagonistic transcription factor modules. Moreover, proteomics analysis revealed that SMs altered the abundance of proteins associated with cell cycle, mitochondrial activity, and the balance between canonical and noncanonical NF-κB signaling. Whereas SMs inhibited interleukin-17 (IL-17) production and ameliorated …

bcl-2 expression and prognosis in squamous-cell carcinomas of the esophagus

1996

The bcl-2 proto-oncogene is a known inhibitor of apoptosis and may be an important regulator of tumor growth. In the present study, bcl-2-protein expression was investigated by immunohistochemistry and correlated with prognosis in a series of 150 potentially curatively resected squamous-cell carcinomas of the esophagus. For comparison, bcl-2-protein expression was analyzed in normal esophageal mucosa, severe squamous dysplasias and carcinomas in situ. bcl-2 immunoreactivity was found in 40 out of 150 invasive squamous-cell carcinomas; the remaining carcinomas were completely negative. bcl-2-protein expression was found more frequently among poorly differentiated than among well-differentiat…

Frequent Alteration of the Yin Yang 1/Raf-1 Kinase Inhibitory Protein Ratio in Hepatocellular Carcinoma

2011

The transcription factor Yin Yang 1 (YY1) can favor several aspects of tumorigenesis. In turn, Raf-1 Kinase Inhibitor Protein (RKIP) inhibits the oncogenic activities of MAPK and NF-κB pathways and promotes drug-induced apoptosis. Mutual influences between YY1 and RKIP may exist, and there are already separate evidences that relevant increases in YY1 and reductions in RKIP occur in hepatocellular carcinoma (HCC). However, the levels of the two factors have never been concomitantly examined in HCC. We evaluated by RT-PCR the mRNA levels of YY1, YY1AP, RKIP, and survivin in 35 clinical HCCs (91% HCV-related), in their adjacent cirrhotic tissues and in 6 healthy livers. Immunohistochemical ana…

Beta-catenin and surviving expression in keratocystic odontogenic tumor (KCOT). A comparative immunohistochemical study in primary, recurrent and nev…

2013

Aim: To determine the epithelial expression of ß-catenin and survivin in sporadic (primary, and recurrent) and nevoid basal cell carcinoma syndrome (NBCCS) keratocystic odontogenic tumour (KCOT) in order to assess activation of the ß-catenin pathway and evidence of apoptotic inhibition, processes that may contribute to the known differences in their biological behaviour. Materials and Methods: Sections from 40 cases of KCOT (19 sporadic/primary; 9 sporadic/recurrent and 12 NBCCS-associated) were immunohistochemically stained for ß-catenin and survivin. The extent and intensity of immunoreactivity within the lining epithelium was assessed, using semi-quantitative scales, independently by two…