scholarly journals Mitochondrial Localization of Reaper to Promote Inhibitors of Apoptosis Protein Degradation Conferred by GH3 Domain-Lipid Interactions

2007 ◽  
Vol 283 (1) ◽  
pp. 367-379 ◽  
Author(s):  
Christopher D. Freel ◽  
D. Ashley Richardson ◽  
Michael J. Thomenius ◽  
Eugene C. Gan ◽  
Sarah R. Horn ◽  
...  
Keyword(s):  
Protein Degradation ◽  
Mitochondrial Localization ◽  
Inhibitors Of Apoptosis ◽  
Lipid Interactions ◽  
Apoptosis Protein

scholarly journals Targeted Protein Degradation by Chimeric Compounds using Hydrophobic E3 Ligands and Adamantane Moiety

2020 ◽  
Vol 13 (3) ◽  
pp. 34
Author(s):  
Takuji Shoda ◽  
Nobumichi Ohoka ◽  
Genichiro Tsuji ◽  
Takuma Fujisato ◽  
Hideshi Inoue ◽  
...  
Keyword(s):  
Protein Degradation ◽  
Inhibitors Of Apoptosis ◽  
Target Proteins ◽  
Aryl Hydrocarbon ◽  
Apoptosis Protein ◽  
Dependent Protein ◽  
New Compounds ◽  
Chimeric Molecules ◽  
Tagging System ◽  
In Cells

Targeted protein degradation using small chimeric molecules, such as proteolysis-targeting chimeras (PROTACs) and specific and nongenetic inhibitors of apoptosis protein [IAP]-dependent protein erasers (SNIPERs), is a promising technology in drug discovery. We recently developed a novel class of chimeric compounds that recruit the aryl hydrocarbon receptor (AhR) E3 ligase complex and induce the AhR-dependent degradation of target proteins. However, these chimeras contain a hydrophobic AhR E3 ligand, and thus, degrade target proteins even in cells that do not express AhR. In this study, we synthesized new compounds in which the AhR ligands were replaced with a hydrophobic adamantane moiety to investigate the mechanisms of AhR-independent degradation. Our results showed that the compounds, 2, 3, and 16 induced significant degradation of some target proteins in cells that do not express AhR, similar to the chimeras containing AhR ligands. However, in cells expressing AhR, 2, 3, and 16 did not induce the degradation of other target proteins, in contrast with their response to chimeras containing AhR ligands. Overall, it was suggested that target proteins susceptible to the hydrophobic tagging system are degraded by chimeras containing hydrophobic AhR ligands even without AhR.

Lysine Covalent Antagonists of Melanoma Inhibitors of Apoptosis Protein

2021 ◽  
Author(s):  
Parima Udompholkul ◽  
Carlo Baggio ◽  
Luca Gambini ◽  
Giulia Alboreggia ◽  
Maurizio Pellecchia
Keyword(s):  
Inhibitors Of Apoptosis ◽  
Apoptosis Protein

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.

scholarly journals Ubiquitin Pathway Is Associated with Worsening Left Ventricle Function after Mitral Valve Repair: A Global Gene Expression Study

2020 ◽  
Vol 21 (14) ◽  
pp. 5073
Author(s):  
Feng-Chun Tsai ◽  
Gwo-Jyh Chang ◽  
Ying-Ju Lai ◽  
Shang-Hung Chang ◽  
Wei-Jan Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mitral Valve ◽  
Mitral Regurgitation ◽  
Protein Degradation ◽  
Left Ventricular ◽  
Contractile Protein ◽  
Lv Function ◽  
Protein Ubiquitination ◽  
Bmp Receptors ◽  
Apoptosis Protein

The molecular mechanism for worsening left ventricular (LV) function after mitral valve (MV) repair for chronic mitral regurgitation remains unknown. We wished to assess the LV transcriptome and identify determinants associated with worsening LV function post-MV repair. A total of 13 patients who underwent MV repair for chronic primary mitral regurgitation were divided into two groups, preserved LV function (N = 8) and worsening LV function (N = 5), for the study. Specimens of LV from the patients taken during surgery were used for the gene microarray study. Cardiomyocyte cell line HL-1 cells were transfected with gene-containing plasmids and further evaluated for mRNA and protein expression, apoptosis, and contractile protein degradation. Of 67,258 expressed sequence tags, microarrays identified 718 genes to be differentially expressed between preserved-LVF and worsening-LVF, including genes related to the protein ubiquitination pathway, bone morphogenetic protein (BMP) receptors, and regulation of eIF4 and p70S6K signaling. In addition, worsening-LVF was associated with altered expressions of genes pathologically relevant to heart failure, such asdownregulated apelin receptors and upregulated peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A). HL-1 cardiomyocyte cells transfected with ubiquitination-related genes demonstrated activation of the protein ubiquitination pathwaywith an increase in the ubiquitin activating enzyme E1 (UAE-E1). It also led to increased apoptosis, downregulated and ubiquitinated X-linked inhibitor of apoptosis protein (XIAP), and reduced cell viability. Overexpression of ubiquitination-related genes also resulted in degradation and increased ubiquitination of α-smooth muscle actin (SMA). In conclusion, worsening-LVF presented differential gene expression profiles from preserved-LVF after MV repair. Upregulation of protein ubiquitination-related genes associated with worsening-LVF after MV repair may exert adverse effects on LV through increased apoptosis and contractile protein degradation.

scholarly journals Aryl-fluorosulfate-based Lysine Covalent Pan-Inhibitors of Apoptosis Protein (IAP) Antagonists with Cellular Efficacy

2019 ◽  
Vol 62 (20) ◽  
pp. 9188-9200 ◽  
Author(s):  
Carlo Baggio ◽  
Parima Udompholkul ◽  
Luca Gambini ◽  
Ahmed F. Salem ◽  
Jennifer Jossart ◽  
...  
Keyword(s):  
Inhibitors Of Apoptosis ◽  
Apoptosis Protein
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