• r\nThat's what took the team down the road of targeting BCL-2 family of proteins, also called B-cell lymphoma two, a pro survival protein that keeps a cell alive. (abbvie.com)
  • Communication between the cell survival pathway of autophagy and the cell death pathway of apoptosis is crucial for determining the best outcome for the cell, and ultimately its fate. (edu.au)
  • However, recent studies have suggested that BRAFi/MEKi and ERK1/2i resistance can arise through activation of a parallel signalling pathway leading to activation of ERK5, an unusual protein kinase that contains both a kinase domain and a transcriptional transactivation domain. (babraham.ac.uk)
  • Recent studies have demonstrated that pharmacological inhibition of the Notch pathway with γ-secretase inhibitor (GSI) induces apoptosis of multiple myeloma (MM) cells via upregulation of the proapoptotic protein Noxa. (aacrjournals.org)
  • Cancer cells hijack the survival arm of the BCL-2 family pathway to suppress the cell killing proteins and thereby enforce an immortal state. (alexslemonade.org)
  • These data uncovered the IL32β/BAFF axis as a previously undescribed pathway involved in lymphoma-associated macrophage polarization and tumor survival, which could be counteracted through selective NIK inhibition. (haematologica.org)
  • To achieve the effects of controlling cell fate, small molecules have been developed to compensate for the imbalance between pro- and antiapoptotic BCL-2 proteins and restore the apoptotic pathway. (chemdiv.com)
  • Thus, we found that broad and multimodal targeting of the BCL-2 family pathway can overcome pathologic barriers to cell death. (peptide.com)
  • and the intrinsic pathway, which is activated by cellular stress and is regulated primarily at the level of mitochondria by the Bcl-2 family of proteins ( Fig. 1 ). (biologists.com)
  • The intrinsic apoptotic pathway is initiated in response to a variety of stress signals ( Willis and Adams, 2005 ), and a complex interplay of Bcl-2 proteins relays this signal to the mitochondrial outer membrane (OM) to initiate Bak and Bax activation, oligomerisation and OM damage ( Fig. 1 ). (biologists.com)
  • However, in certain cell types, the extrinsic pathway also induces mitochondrial damage by cleaving the pro-apoptotic Bcl-2 family protein Bid to its activated truncated form (tBid), which leads to Bak and Bax activation. (biologists.com)
  • Pathway inference tools were used to interpret these proteins in terms of functionally enriched pathways in the tumor cell lines. (biomedcentral.com)
  • However, relating gene expression with the specific role that the corresponding protein plays in a signaling pathway is complicated by post-transcriptional control of protein expression [ 8 ] and tight regulation of protein activity [ 9 ]. (biomedcentral.com)
  • In the present study, we observed that inactivation of the ERK1/2 signaling pathway using ABT-737 dramatically increased the expression of pro-apoptotic protein Bim via transcriptional and/or posttranslational regulation, in a cell type-dependent manner, inducing mitochondria-mediated apoptosis of human oral cancer cells. (oncotarget.com)
  • BCL2 proteins are described as 'crucial regulators of apoptosis' (PMID:15868100)and the intrinsic apoptosis pathway is initiated by the release of mitochondrial cytochrome c into the cytoplasm, which results in the activation of caspases (15102863) - help in generating a defintion for intrinsic apoptosis? (geneontology.org)
  • Cells possess distinct pathways that promote their survival or death. (edu.au)
  • The first is to use an in vivo approach to analyse transgenic mice in which the autophagy regulator known as Beclin has been engineered to either disrupt or enhance its regulation by key components (i.e. proteins) of the apoptosis pathways. (edu.au)
  • Akt1 is involved in cellular survival pathways, by inhibiting apoptotic processes. (wikipedia.org)
  • Akt1 is also able to induce protein synthesis pathways, and is therefore a key signaling protein in the cellular pathways that lead to skeletal muscle hypertrophy and general tissue growth. (wikipedia.org)
  • Rhamnaceae) on cisplatin-induced damage to kidney epithelial LLC-PK1 cells via mitogen-activated protein kinase (MAPK) and apoptosis pathways. (mdpi.com)
  • These effects were associated with inhibition of the mitogen‑activated protein kinase/extracellular signal‑regulated kinase 1/2 and protein kinase B signaling pathways. (spandidos-publications.com)
  • The underlying mechanisms of these effects were primarily mediated by G 1 phase cell cycle arrest and inhibition of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulate kinase 1/2 (Erk 1/2) and protein kinase B (Akt) signaling pathways. (spandidos-publications.com)
  • Cancer cells subvert the natural balance between cellular life and death, achieving immortality through pathologic enforcement of survival pathways and blockade of cell death mechanisms. (peptide.com)
  • The VEGF-mediated decrease in amyloid beta is dependent on a functional Flt-1 receptor and is inhibited by dicoumarol a multifunctional inhibitor of stress activated protein kinase (SAPK)/JNK and NFkappaB pathways. (bioinf.org)
  • Many signaling pathways that affect neuronal survival/death decisions converge downstream on common targets. (bioinf.org)
  • The objectives of this study were to quantify alterations in protein expression in two HER2+ cellular models of breast cancer and to infer differentially regulated signaling pathways in these models associated with the hallmarks of cancer. (biomedcentral.com)
  • We observed "protein ubiquitination" and "apoptosis signaling" pathways were both enriched in the two breast cancer models while "IGF signaling" and "cell motility" pathways were enriched in BT474 and "amino acid metabolism" were enriched in the SKBR3 cell line. (biomedcentral.com)
  • While "protein ubiquitination" and "apoptosis signaling" pathways were common to both the cell lines, the observed patterns of protein expression suggest that the evasion of apoptosis in each tumorigenic cell line occurs via different mechanisms. (biomedcentral.com)
  • High-throughput quantitative proteomic analysis has previously been used to identify differentially expressed proteins and pathways associated with breast tumor phenotypes [ 12 ]. (biomedcentral.com)
  • Therefore, there have been recent attempts to develop effective anticancer strategies targeting apoptotic signaling pathways [ 2 ], such as through inhibiting anti-apoptotic survival factors, which are likely overexpressed in many tumors and may confer drug-resistant phenotypes [ 2 , 3 ]. (oncotarget.com)
  • Additionally, the anti-apoptotic protein Bcl-2 was elevated prompting us to study the effect of LTD4 on survival and apoptosis. (lu.se)
  • Docetaxel, in addition to stabilizing microtubules, also induces apoptosis by downregulating antiapoptotic proteins. (oncologynurseadvisor.com)
  • Pro-apoptotic BCL-2 family proteins are frequently disarmed in relapsed and refractory cancer through genetic deletion or interaction-based neutralization by overexpressed antiapoptotic proteins, resulting in resistance to chemotherapy and radiation treatments. (peptide.com)
  • Furthermore, we found that levels of phosphorylated MEK1/2 and ERK1/2 were decreased in cyclin I-deficient podocytes and that inhibition of MEK1/2 restored Bcl2 and Bcl-XL protein levels. (jci.org)
  • C1QBP significantly increased ROS level, apoptosis, and the expression of apoptotic proteins such as cleaved caspase-3 and bax/bcl2 via regulating XDH. (medsci.org)
  • Instead, BH3-only proteins appear to control apoptosis by neutralizing pro-survival Bcl2 family members. (the-scientist.com)
  • Since BCL2, a protein that indirectly inhibits cell apoptosis, is required for certain chemotherapies to work, the absence of BCL2 obscures their uses in prostate cancer. (oncologynurseadvisor.com)
  • 69 BCL2 expression was noted to be an independent predictor of survival in patients treated with taxanes. (oncologynurseadvisor.com)
  • During treatment with taxanes, BCL2 is phosphorylated, which prevents heterodimerization with other BCL family genes, thereby promoting apoptosis. (oncologynurseadvisor.com)
  • 71 Clusterin is a small heat shock glycoprotein overexpressed in most of the solid tumors, which promotes apoptosis by binding to various molecules such as BAX (BCL2-associated X protein) 72 and signal transducer and activator of transcription (STAT)−1. (oncologynurseadvisor.com)
  • In vivo experiments using xenograft and SCID-hu models of MM demonstrated a significant antitumor effect of the GSI/ABT-737 combination as compared to the effect of Notch or Bcl-2/Bcl-xL inhibitors alone. (aacrjournals.org)
  • In contrast, BH3 mimetics without BCL-XLi activity, conventional chemotherapy, and MEK inhibitors show no effect. (ibecbarcelona.eu)
  • Inhibitors of apoptosis proteins (IAPs), mainly survivin and X-linked inhibitor of apoptosis (XIAP) prevent the processing of procaspase 3 to caspase 3, thereby inhibiting apoptosis. (oncologynurseadvisor.com)
  • By impairing the develop- with specific inhibitors, markedly improves survival in ment of adaptive immune responses needed for recovery, murine sepsis models. (cdc.gov)
  • Bcl-2 is antiapoptotic), and other inhibitors (Figure 1). (cdc.gov)
  • The directed expression of Buffy in the dopamine producing neurons, via aDdc-Gal4 transgene, resulted in flies with increased climbing ability and enhanced survival, while the inhibition of Buffy in the dopaminergic neurons reduced climbing ability over time prematurely, similar to the phenotype observed in the alpha-synuclein-induced Drosophila model of PD. (sdbonline.org)
  • A set of twenty-five thioxanthene-9-one and xanthene-9-one derivatives, that were previously shown to inhibit cholinesterases (ChEs) and amyloid β (Aβ40) aggregation, were evaluated for the inhibition of tau protein aggregation. (ibecbarcelona.eu)
  • Finally, we demonstrated the efficacy of selective NIK/alternative-NFkB inhibition to counteract microenvironment-dependent induction of IL32β and BAFF-dependent survival of MCL cells. (haematologica.org)
  • Thus, selective inhibition of pro-survival proteins can induce death of HIV-1-infected cells that persist on ART, extending time to viral rebound. (ehpv.ee)
  • In comparison, the inhibition of autophagy reduced the phrase amounts of ATG protein in the tissue targeted by NDV. (immune-source.com)
  • BH3 mimetics with high affinity for BCL-XL (BCL-XLi) reduce metabolic activity and induce mitochondrial apoptosis in senescent PA cells at nano-molar concentrations. (ibecbarcelona.eu)
  • A hydrocarbon-stapled peptide modeled after the BIM BH3 helix broadly targeted BCL-2 family proteins with high affinity, blocked inhibitory antiapoptotic interactions, directly triggered proapoptotic activity, and induced dose-responsive and BH3 sequence-specific cell death of hematologic cancer cells. (peptide.com)
  • Among the numerous available small molecule BH3 mimetics, ABT-737, a potent small molecule that binds to Bcl-2/Bcl-xL with high affinity, has anti-tumor activity in a wide variety of cancer cells. (oncotarget.com)
  • Both proteins can localize at the mitochondrion , but the way they control apoptosis still remains unclear. (sdbonline.org)
  • These results provide a mechanism by which Drosophila Bcl-2 family proteins can control apoptosis and shed light on a link between Rbf1 and mitochondrial dynamics, in vivo. (sdbonline.org)
  • ABT-737, a novel BH3 mimetic, was shown to block Bcl-2 and Bcl-xL and induce MM cell apoptosis. (aacrjournals.org)
  • Despite early optimism, it is apparent that transcriptional reactivation of latently infected cells is not sufficient to induce cell death and delay viral rebound, and recent evidence suggests that antiapoptotic mechanisms are in place that maintain survival of latently infected cells despite the highly apoptotic environment of productive infection. (ehpv.ee)
  • Protein kinase B (PKB), also known as Akt, is the collective name of a set of three serine/threonine-specific protein kinases that play key roles in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription, and cell migration. (wikipedia.org)
  • There are three different genes that encode isoforms of Protein kinase B. These three genes are referred to as AKT1, AKT2, and AKT3 and encode the RAC alpha, beta, and gamma serine/threonine protein kinases respectively. (wikipedia.org)
  • For example, PI 3-kinases may be activated by a G protein coupled receptor or receptor tyrosine kinase such as the insulin receptor. (wikipedia.org)
  • mTORC2 therefore functionally acts as the long-sought PDK2 molecule, although other molecules, including integrin-linked kinase (ILK) and mitogen-activated protein kinase-activated protein kinase-2 (MAPKAPK2) can also serve as PDK2. (wikipedia.org)
  • Studies have suggested that cAMP-elevating agents could also activate Akt through protein kinase A (PKA) in the presence of insulin. (wikipedia.org)
  • Background Pilocytic astrocytoma (PA) is the most common pediatric brain tumor and a mitogen-activated protein kinase (MAPK)-driven disease. (ibecbarcelona.eu)
  • A. Total protein was extracted and western blot analysis performed using specific antibodies for phosphorylated p38 MAP kinase total p38 MAP kinase and GAPDH. (bioinf.org)
  • Data are normalized … Experiments to determine the activity of phophorylated p38 MAP kinase were performed using the ATF-2 fusion protein as a substrate and its level detected by western blot analysis. (bioinf.org)
  • Dissociation of VEGF effects on p38 MAP kinase activity and on neuronal survival We examined the ability of VEGF to affect p38 MAP kinase activity as indicated by ATF-2 phosphorylation (Fig. 3A) and neuronal survival (Fig. 3B) in the presence of a p38 MAP kinase inhibitor (SB203580) or the p38 MAP kinase activator anisomycin. (bioinf.org)
  • It has been previously shown that rbf1 pro-apoptotic activity depends on its ability to decrease the level of anti-apoptotic proteins such as the Bcl-2 family protein Buffy. (sdbonline.org)
  • Taken together these data demonstrate that this Dioscin (Collettiside III) neurotrophic effects of VEGF are likely mediated directly by increasing Dioscin (Collettiside III) survival and decreasing apoptotic proteins and signals as well as indirectly by modulating release of proteins that affect neuronal viability. (bioinf.org)
  • PMID:14996496, table 1 provides links to papers that describe subcellular location of many pro- and anti-apoptotic proteins. (geneontology.org)
  • A specialized group of proteins, called the BCL-2 family, regulates the natural balance between cellular life and death, ensuring that essential cells are preserved and damaged cells eliminated. (alexslemonade.org)
  • neurons VEGF also regulates release of proteins that affect neuronal viability. (bioinf.org)
  • BAD (Bcl-2 antagonist of cell death, Bcl-2 associated death promoter) is a pro-apoptotic member of the Bcl-2 protein family that is regulated by phosphorylation in response to survival factors. (uni-wuerzburg.de)
  • Although much attention has been devoted to the identification of phosphorylation sites in murine BAD (mBAD), little data are available with respect to phosphorylation of human BAD (hBAD) protein. (uni-wuerzburg.de)
  • In addition, using surface plasmon resonance technique we analyzed the direct consequences of hBAD phosphorylation by RAF with respect to complex formation of BAD with 14-3-3 proteins and Bcl-XL. (uni-wuerzburg.de)
  • Phosphorylation of hBAD by active RAF promotes 14-3-3 protein association, whereby the phosphoserine 99 represents the major binding site. (uni-wuerzburg.de)
  • This pore-forming capacity is dependent on phosphorylation status and interaction with 14-3-3 proteins. (uni-wuerzburg.de)
  • Furthermore, we identified hBAD serine 134 to be strongly involved in survival signaling in B-RAF-V600E containing tumor cells and found phosphorylation of this residue to be crucial for efficient proliferation in these cells. (uni-wuerzburg.de)
  • Furthermore, in influenza A virus-infected cells, TG6-44 treatment led to suppression of virus-induced cell death as evidenced by decreased caspase-3 activation, decreased proportion of Annexin V+PI+ cells, and increased Bcl-2 phosphorylation. (cdc.gov)
  • BH3 mimetics are small-molecule therapeutics that lower the threshold for induction of intrinsic apoptosis by antagonizing the function of Bcl-2 family pro-survival proteins. (ehpv.ee)
  • Obatoclax is a small-molecule inhibitor of the Bcl-2 family of proteins, including the key protein Mcl-1. (lungevity.org)
  • Obatoclax, Gemin X's potential first-in-class small molecule antagonist of Bcl-2, is specifically designed to inhibit all relevant members of the Bcl-2 family of proteins, including the dominant member, Mcl-1. (lungevity.org)
  • BAD (Bcl-2 antagonist of cell death, Bcl-2 associated death promoter) ist ein pro-apoptotisches Mitglied der Bcl-2 Proteinfamilie und wird in Abhängigkeit von Wachstumsfaktoren durch Phosphorylierung reguliert. (uni-wuerzburg.de)
  • We view this unique Bcl-2 inhibitor - an antagonist of all of the relevant Bcl-2 prosurvival proteins - as having important and broad applicability in cancer treatment," said Jean Viallet, M.D., Chief Medical Officer at Gemin X. "We are very encouraged by the 100% response rate seen in these previously untreated SCLC patients who enrolled in this Phase 1b trial. (lungevity.org)
  • Only two Bcl-2 family genes have been found in Drosophila melanogaster including the pro-cell survival, human Bok-related orthologue, Buffy. (sdbonline.org)
  • Aberrations of AR, erythroblast transformation-specific ( ETS ) genes, Tumor protein 53 (TP53), and Phosphatase and tensin homolog (PTEN) occurred in 40%-60% of 150 mCRPC cases in a recent study. (oncologynurseadvisor.com)
  • GO-AgNPs induced significant cytotoxicity by the loss of cell viability, production of reactive oxygen species (ROS), cell cycle arrest, increasing leakage of lactate dehydrogenase (LDH) and level of Malondialdehyde (MDA), increasing expression of pro-apoptotic genes and decreasing expression of anti-apoptotic genes. (researchsquare.com)
  • MCL-1 is a pro-survival BCL-2 family member that has emerged as a ubiquitous chemotherapy and radiotherapy resistance factor in pediatric cancer. (alexslemonade.org)
  • Venetoclax is a BH3 mimetic that specifically antagonizes Bcl-2 and is approved for the treatment of chemotherapy-refractory chronic lymphocytic leukemia (CLL). (ehpv.ee)
  • Mechanistically, both peptides caused a significant reduction at G0/G1 phase, in correlation with an augmented expression of the cell cycle inhibitory proteins p53, p27, p21, necrosis, exacerbated generation of reactive oxygen species and diminished mitochondrial membrane potential, all hallmarks of cellular stress. (nature.com)
  • RNA viruses may escape acquired humoral and cellular immune responses by mutations in protective antigenic epitopes (e.g., avian influenza viruses), while accessory nonstructural proteins or multifunctional structural proteins interfere with the interferon system (e.g. (imperial.ac.uk)
  • Mitochondrial porin , also known as the voltage-dependent anion channel (VDAC), is a multi-functional channel protein that shuttles metabolites between the mitochondria and the cytosol and implicated in cellular life and death decisions. (sdbonline.org)
  • Given the critical roles of BCL-2 family proteins in maintaining cellular homeostasis, perturbation of the complexes between pro- and antiapoptotic BCL-2 proteins or their levels of expression could alter the cellular homeostatic balance and lead to overcoming apoptosis. (chemdiv.com)
  • The aim was to identify cellular and cytogenetic markers of prognostic relevance to survival of high-risk MDS cases. (who.int)
  • Our hypothesis is that Bcl-2 pro-survival proteins provide a survival advantage for melanomas and might contribute to resistance to standard chemotherapeutic drugs. (edu.au)
  • Among the many regulatory factors, overexpression of pro-survival Bcl-2 family members may promote resistance to chemotherapeutic drugs in many tumors. (oncotarget.com)
  • Therefore, there is substantial interest in developing chemotherapeutic drugs that directly target pro-survival Bcl-2 proteins by mimicking the BH3 domain and unleashing pro-apoptotic molecules in tumor cells. (oncotarget.com)
  • Complementary projects in the lab focus on autophagy, a cell survival process that has significant cross-talk with apoptosis. (edu.au)
  • There is some evidence that Bcl-2 pro-survival proteins (which normally keep cells alive by inhibiting the cell death program of apoptosis) are expressed at unusually high levels in melanoma compared to normal melanocytes. (edu.au)
  • This will be achieved through the use of Bcl-2 protein-selective reagents, which were engineered in the Fairlie laboratory, to profile melanoma cell lines, as well as samples from patients. (edu.au)
  • Results from this work will significantly advance our understanding of how the interplay between cell death and cell survival is regulated, which is still poorly understood despite its considerable biological importance. (edu.au)
  • Since it can block apoptosis and thereby promote cell survival, Akt1 has been implicated as a major factor in many types of cancer. (wikipedia.org)
  • ABT-199 is based on a landmark discovery made in the late 1980s by Walter and Eliza Hall Institute scientists that a protein called Bcl-2 promoted cancer cell survival . (edu.au)
  • Signaling through the receptor/transcriptional regulator Notch plays an important role in tumor cell survival. (aacrjournals.org)
  • Taken all together this demonstrates a role for Buffy, a Bcl-2 pro-cell survival gene, in neuroprotection. (sdbonline.org)
  • Immunoprecipitation of BMF protein from NCI-H209 cell extracts. (cellsignal.com)
  • E4 significantly prevented the reduction of the b-wave and oscillatory potential amplitudes and retinal cell loss and maintained the Bcl-2/Bax and Bcl-xL/Bax ratio balances in GK rats. (molvis.org)
  • The flexibility to control the survival and demise of a cell is paramount all through the lifespan of a multicellular organism. (eumorphia.org)
  • Apoptosis, a foremost physiological type of programmed cell demise, is regulated by the Bcl-2 household proteins which are both pro-apoptotic or pro-survival. (eumorphia.org)
  • r\nThat's what took us down the road of really trying to target BCL-2 or B-cell lymphoma two, a pro survival protein that acts to keep a cell alive. (abbvie.com)
  • 70 Mcl1 (myeloid cell leukemia differentiation protein 1) and other members of the BCL family, such as BCL-xl (B-cell lymphoma-extra-large), are also involved in resistance to Interleukin (IL)-6, stromal cell derived factor-1, and cytokine-induced apoptosis. (oncologynurseadvisor.com)
  • Myeloid cell leukemia-1 (MCL-1), a member of antiapoptotic BCL-2 family proteins. (chemdiv.com)
  • The antiapoptotic function of MCL-1 is essential to cell survival and homeostasis. (chemdiv.com)
  • We harnessed the natural killing activity of BCL-2-interacting mediator of cell death (BIM), which contains one of the most potent BH3 death domains of the BCL-2 protein family, to restore BH3-dependent cell death in resistant hematologic cancers. (peptide.com)
  • In bottom line, we confirmed that autophagy brought about by genotype VII NDV infections was important for virus-like replication, NDV-induced apoptosis, and cell survival in buy 480-11-5 chicken cells and tissues. (immune-source.com)
  • A proteomic workflow was used to identify proteins in two HER2 positive tumorigenic cell lines (BT474 and SKBR3) that were differentially expressed relative to a normal human mammary epithelial cell line (184A1). (biomedcentral.com)
  • These include members of the Bcl-2 protein family, course, and extent of programmed cell death will aid man- which have both proapoptotic and antiapoptotic activity agement of patients with severe infections. (cdc.gov)
  • All these events could be reversed by the addition of LTD4, which even could increase cell survival above basal level. (lu.se)
  • We furthermore detected a novel LTD4-induced association between Bcl-2 and the multifacetted protein b-catenin that may encompass a new mode of influencing cell survival. (lu.se)
  • These effects of LTD4 were shown to be mediated through the G-protein coupled receptor, CysLT1 and this strongly indicates that inflammatory mediators such as LTD4 may have large impacts on the state of cell survival regulation. (lu.se)
  • The second aim is to determine whether resistance to current melanoma treatment arises due to elevated levels of Bcl-2 pro-survival proteins, and whether treatment with Bcl-2-targeting molecules will resensitise tumours to standard drugs, informing potential drug treatment combinations. (edu.au)
  • The Drosophila retinoblastoma protein, Rbf1, induces a debcl and drp1 -dependent mitochondrial apoptosis. (sdbonline.org)
  • This study demonstrates that debcl and the pro-fission gene drp1 are necessary downstream of buffy to trigger a mitochondrial fragmentation during rbf1 -induced apoptosis. (sdbonline.org)
  • We focus here on the BCL-2 family of proteins, which regulate mitochondrial-dependent apoptosis. (ca.gov)
  • it both initiates a proteolytic cascade of pro-apoptotic enzymes and damages mitochondrial function. (biologists.com)
  • The current development of anti-cancer agents that target the Bcl-2 protein family is showing considerable promise, although how this targeting triggers Bak and Bax to perform their crucial function of mitochondrial outer membrane permeabilisation (MOMP) is not clear. (biologists.com)
  • Our aim is to develop new reagents, including drugs that could target and inhibit the actions of the key pro-survival protein proteins that keep cancers alive. (edu.au)
  • Studies have suggested the Bcl-2 'survival instinct' may play a role in other cancers, and preclinical testing has suggested drugs that target Bcl-2 could be used to treat other blood cancers, or used in combination with existing treatments to improve treatments for breast, lung and prostate cancers. (edu.au)
  • High levels of Bcl-2 protect the leukaemia cells from dying when using standard treatments," Professor Roberts said. (edu.au)
  • A team of scientists led by Professor Jerry Adams, Professor Suzanne Cory and Professor Andreas Strasser are striving to understand how the protein Bcl-2 keeps cells alive. (edu.au)
  • BH3-mimetics, drugs that block pro-survival proteins such as BCL-2, are shown to kill cancer cells. (edu.au)
  • We hypothesize that a more rapid induction of pro-inflammatory cytokine responses in bursal cells following IBDV infection leads to more severe disease in line W birds than in line 15I. (imperial.ac.uk)
  • While toxic for MM cells, the combination of GSI and ABT-737 did not affect survival of peripheral blood mononuclear cells isolated from healthy donors. (aacrjournals.org)
  • Signaling through the receptor/transcriptional regulator Notch plays an important role in the survival of tumor cells and their protection from apoptosis induced by chemotherapeutic agents. (aacrjournals.org)
  • We previously showed that cyclin I does not regulate proliferation, but rather controls survival of podocytes, terminally differentiated epithelial cells that are essential for the structural and functional integrity of kidney glomeruli. (jci.org)
  • Taken together, these data suggest that a cyclin I-Cdk5 complex forms a critical antiapoptotic factor in terminally differentiated cells that functions via MAPK signaling to modulate levels of the prosurvival proteins Bcl-2 and Bcl-XL. (jci.org)
  • rbf1 , the Drosophila homolog of Rb , also displays a pro- apoptotic activity in proliferative cells. (sdbonline.org)
  • Dependence of senescent PA cells on anti-apoptotic BCL-2 members was investigated using a comprehensive set of BH3 mimetics. (ibecbarcelona.eu)
  • Results Senescent PA cells upregulate BCL-XL upon senescence induction and show dependency on BCL-XL for survival. (ibecbarcelona.eu)
  • Conclusions Our data demonstrate that BCL-XL is critical for survival of senescent PA tumor cells and provides proof-of-principle for the use of clinically available BCL-XL-dependent senolytics. (ibecbarcelona.eu)
  • Using ex vivo models of primary MCL cells (n=23), we demonstrated that, through the secretion of IL32β, the tumor was able to polarize monocytes into specific MCL-associated macrophages, which in turn favor tumor survival. (haematologica.org)
  • Human Embryonic Stem Cells Express Elevated Levels of Multiple Pro-Apoptotic BCL-2 Family Members. (ca.gov)
  • We used quantitative PCR to compare the steady-state expression profile of all human BCL-2 family members in hESCs with that of human primary cells from various origins and two cancer lines. (ca.gov)
  • Our findings indicate that hESCs express elevated levels of the pro-apoptotic BH3-only BCL-2 family members NOXA, BIK, BIM, BMF and PUMA when compared with differentiated cells and cancer cells. (ca.gov)
  • Using a humanized mouse model of HIV-1 infection and CD4 + T cells from PLWH on ART, we investigate whether antagonizing host pro-survival proteins can prime latent cells to die and facilitate HIV-1 clearance. (ehpv.ee)
  • Venetoclax, a pro-apoptotic inhibitor of Bcl-2, depletes total and intact HIV-1 DNA in CD4 + T cells from PLWH ex vivo . (ehpv.ee)
  • This venetoclax-sensitive population is enriched for cells with transcriptionally higher levels of pro-apoptotic BH3-only proteins. (ehpv.ee)
  • Although antiretroviral therapy (ART) suppresses HIV-1 replication, pro-virus can persist in long-lived and proliferating CD4 + T cells and is the likely source of rapid viral rebound when ART is interrupted. (ehpv.ee)
  • Our results suggest that although trisomy 8 cells are in a pro-apoptotic state, they are checked by the enhanced expression of anti-apoptotic signals which provide them with their proliferative advantage. (who.int)
  • Notably, in the presence of wild type hBAD, co-expression of survival kinases, such as RAF and PAK1, leads to a strongly increased proliferation, whereas substitution of serine 134 by alanine abolishes this process. (uni-wuerzburg.de)
  • 0.01) and, when stimulated ex vivo with LPS, showed more rapid up-regulation of pro-inflammatory gene expression than those from line 15I birds. (imperial.ac.uk)
  • In addition, levels of the prosurvival proteins Bcl-2 and Bcl-XL were reduced in podocytes and neurons from cyclin I-deficient mice, and restoration of Bcl-2 or Bcl-XL expression prevented injury-induced apoptosis. (jci.org)
  • C1QBP promoted the mRNA and protein expression of hypoxanthine catabolic enzyme XDH. (medsci.org)
  • It also downregulated the expression of glial fibrillary acidic protein and reduced retinal reactive gliosis. (molvis.org)
  • We determined expression of anti-apoptotic BCL-2 members in these models and primary PA. (ibecbarcelona.eu)
  • However, compensatory expression of pro-survival BCL-2 family members in hESCs was not observed, suggesting a possible explanation for the elevated rates of apoptosis observed in proliferating hESC cultures, as well as a mechanism that could be exploited to limit hESC-derived neoplasms. (ca.gov)
  • In contrast to genomic-based assays, proteomics provides an attractive platform to profile this regulatory layer of protein activity and differences in the level of protein expression [ 10 ]. (biomedcentral.com)
  • In the last decade, diagnostic and prognostic evaluation has been facilitated by global gene expression profiling (GEP), provid- ing a new powerful means for the classification, prediction of survival, and response to treatment of lym- phomas. (lu.se)
  • In this Commentary, we discuss the implications of these findings for the regulation of apoptosis by Bcl-2 family proteins. (biologists.com)
  • The key regulator of this process, hypoxia inducible factor 1 (HIF-1), can initiate apoptosis by inducing high concentrations of proapoptotic proteins, such as BNIP3, and can cause stabilisation of p53. (bmj.com)
  • This aim will also explore whether immunotherapy approaches could benefit from Bcl-2 targeting. (edu.au)
  • Recently, with the advent of immunotherapy and anti-angiogenesis therapy, the survival of RCC patients has been improved[ 4 ]. (medsci.org)
  • however, the pore complexes that are formed by Bak and Bax remain poorly defined in terms of their composition, size, number and structure, as well as the mechanism by which they are regulated by other Bcl-2 family members. (biologists.com)
  • The BH3:groove interaction within Bak homodimers supports a general model to explain the associations between Bcl-2 family members. (biologists.com)
  • Immunochemistry staining of arterial vessels detected TGFBIp and the platelet-specific protein GPVI in the vessel wall.We demonstrate for the first time that platelet TGFBIp release is significantly increased in MI and correlates with the severity of acute coronary syndromes (STEMI, NSTEMI). (bvsalud.org)
  • This is accomplished at the molecular level by a specialized surface on survival proteins, called the "anti-apoptotic groove," which neutralizes a helically-shaped motif, called "the BH3 domain," essential to the killing activity of the death proteins. (alexslemonade.org)
  • citation needed] The Akt proteins possess a protein domain known as a PH domain, or pleckstrin homology domain, named after pleckstrin, the protein in which it was first discovered. (wikipedia.org)
  • Clinical trials of an anti-cancer drug for leukaemia begin, vindicating 25 years of Bcl-2 research. (edu.au)
  • Complement component 1 Q subcomponent binding protein (C1QBP) plays a vital role in the progression and metabolism of cancer. (medsci.org)
  • Five-year survival rates of patients with early oral cancer are between 55 and 60%, and decrease to 30-40% in cases of advanced oral cancer. (spandidos-publications.com)