Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 39 for “"Mcl-1"”.
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BAD and Mcl-1 Regulation in Prostate Cancer
… combination treatment causes a rapid decrease of Mcl-1 levels in androgen-independent C42 prostate cancer cells as well as other PTEN-deficient cancer cell lines. Based on this preliminary finding, we hypothesize that simultaneous BAD dephosphorylation and loss of Mcl-1 expression induce rapid …
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Rapid turnover of McL-1 couples translation to cell survival and apoptosis
… role for the anti-apoptotic Bcl-2 family protein Mcl-1, which is rapidly lost following translation inhibition with a half-life of approximately 30 minutes, preceding Bak/Bax activation and detection of cell death. Overexpression of Mcl-1 abrogated cycloheximide-induced apoptosis, while knockdown …
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Flexibility and specificity of the interaction of MCL-1 with BIM BH3
… proteins. I report X-ray crystal structures of MCL-1 in complex with peptides of wild-type and three point mutant sequences of BIM BH3. Together, these structures exhibit a range of conformations within the complex. Structural change with respect to wild-type is most dramatic for an …
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Concomitant Inhibition of Flt3 and Mcl-1 In Flt3 Mutated Acute Myeloid Leukemia
<p>The MCL-1 inhibitor S63845 synergizes with the FLT3 inhibitor midostaurin for potent anti-leukemic effect in preclinical human models of FLT3-ITD mutated acute myeloid leukemia (AML). Acute Myeloid leukemia (AML) is a neoplastic blood disorder defined by a characteristically rapid growth rate …
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The Role of MCL-1 in the Heart: Gateway from Life to Death
<p>MCL-1 is an essential BCL-2 family member that promotes the survival of multiple cellular lineages, but its role in cardiac muscle has remained unclear. Here, we have demonstrated that cardiac-specific ablation of Mcl-1 results in a rapidly fatal, dilated cardiomyopathy preceded by loss of …
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Revealing a Non-canonical Role of Anti-apoptotic MCL-1 in Early Embryonic Development
<p>MCL-1, a well-known pro-survival BCL-2 family member, is indispensable for the survival of various cellular lineages and is also among the most frequently amplified genes in a variety of human malignancies. Gene ablation studies previously revealed that Mcl-1 deficiency leads to embryonic …
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Anti-apoptotic MCL-1 Localizes to the Mitochondrial Matrix and Couples Mitochondrial Fusion to Respiration
<p>MCL-1, an anti-apoptotic BCL-2 family member that is essential for the survival of multiple cell lineages, is also among the most highly amplified genes in cancer. Although MCL-1 is known to oppose cell death, precisely how it functions to promote survival of normal and malignant cells is poorly …
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The Heme-Regulated Inhibitor Pathway Modulates Susceptibility of Poor Prognosis B-Lineage Acute Leukemia to BH3-Mimetics
<p>Anti-apoptotic MCL1 is one of the most frequently amplified genes in human cancers and its elevated expression confers resistance to many therapeutics including the BH3-mimetic agents ABT-199 and ABT-263. The anti-malarial, dihydroartemisinin (DHA) translationally represses MCL-1 and synergizes …
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Targeting Apoptotic Pathways to Overcome Drug Resistance In Acute Myeloid Leukemia
… Despite the initial success, we find that MCL-1 protein renders cancer cells resistant to ABT-199. Next we investigated whether p53 activation could overcome MCL-1–mediated resistance to BCL-2 inhibitor ABT-199. We demonstrate that p53 activation by MDM2 inhibitor RG7388 effectively …
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Vesicular stomatitis virus induced apoptosis occurs by a mechanism involving the activation of pro-apoptotic Bcl-2 proteins Bak and Bid and the inactivation of anti-apoptotic Bcl-2 proteins Bcl-XL and Mcl-1
… inactivation of both antiapoptotic proteins Mcl-1 and Bcl-XL is required. The inactivation of Mcl-1 involves loss of the protein due to inhibition of new host gene expression, while inactivation of Bcl-XL involves the activation of a BH3-only protein, presumably Bid. In the second part of my …
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Biochemical Pathways in Apoptosis
… is the complete disappearance of the mRNA of Mcl-1, an anti-apoptotic member of the Bcl-2 family. This event leads to the elimination of Mcl-1 protein from cells due to the short half-life of its protein. The block or delay of Mcl-1 disappearance by either proteasome inhibitors or Mcl-1 …
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Approaches for Enhancing Therapeutic Efficacy of a Novel IL-10 Gene Family Member: MDA-7/IL-24
… Unfortunately, due to the unique structure of Mcl-1 as compared with Bcl-2 and Bcl-xL, currently employed inhibitors, such as ABT-737 or its clinical counterpart, ABT-263, display limited affinity for Mcl-1. Using nuclear magnetic resonance (NMR) binding assays and computational docking …
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Characterization of Tcl1-Tg:P53-/- Mice That Resemble Human Chronic Lymphocytic Leukemia With 17P-Deletion
… associated with a substantial up-regulation of Mcl-1, suggesting that the p53-miR15a/16-Mcl-1 axis may play an important role in CLL pathogenesis. Interestingly, we also found that loss of p53 resulted in a significant decrease in expression of the miR-30 family especially miR-30d in leukemia …
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Effect of Combination of Aspirin and TRAIL in HeLa Cervical Cancer Cells
… activation of ERK decreased and additionally, Mcl-1 also decreased in combination treatment. Conclusion: TRAIL in combination with aspirin significantly increase apoptosis in HeLa cells through caspase-and mitochondrial-dependent pathway. Mechanism of such a promoted apoptotic effect might be …
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Actions of Pi3K-Delta Inhibitor, Idelalisib, and Its Combination With Bendamustine In Chronic Lymphocytic Leukemia
… in global RNA synthesis and a decline in Mcl-1 transcript and protein levels, with no changes to Bcl-2 protein and mRNA expression. Interestingly, we observed that idelalisib induced γH2AX, a hallmark for DNA damage and repair response.</p> <p>Bendamustine is a FDA approved alkylating …
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Mechanismen der Toxoplasma-gondii-vermittelten Inhibierung der Apoptose in humanen Wirtszelllinien
… vermindert T. gondii die Herunterregulation der Mcl-1-Expression nach Apoptoseinduktion. Das führt dazu, dass trotz Apoptoseinduktion die Translokation von Cytochrom c aus den Mitochondrien in das Zytoplasma inhibiert wird und daraufhin die Caspasen 9 und 3 sowie deren Substrate weniger stark …
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Taspase1 is a Non-oncogene Mediator of Tumorigenesis and Maintenance
… the anti-apoptotic BCL-2 family member MCL-1. Decreased levels of MCL-1 in glioblastoma and melanoma due to Taspase1 loss sensitizes these cells to a variety of apoptotic stimuli, including anoikis, DNA damaging agents etoposide and doxorubicin, and to a targeted inhibitor of BCL-2 …
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The role of TNFAIP1 in regulation of LPS/TNF-ɑ-induced signaling pathway
… Claspin, Cytochromic, HO-1/HMOX1/HSP32, MCL-1, P27/Kip1, or SMAC/Diablo; 5. TNFAIP1 promoter DNA was cloned into pGL3 basic plasmid DNA to determine promoter activity. TNFAIP1 promoter activity was tested via its potential protein-protein interaction using luciferase gene expression. With …
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Inhibition of Deubiquitinase Activity and Ubiquitination of Jak2 Blocks Cytokine Signaling and Induces Tumor Cell Apoptosis
… up-regulation of pro-apoptotic proteins, such as MCL-1 and p53 respectively. Our results demonstrate that chemical modification of a previously described Jak2 inhibitor results in the unexpected discovery of a novel compound which acts as a DUB inhibitor, suppressing Jak-Stat signaling by a novel …
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Ehrlichia chaffeensis E3 Ligase TRP120 Ubiquitinates Tumor Suppressor FBW7 for Degradation to Promote Infection
… network of oncoproteins (Notch, cyclin E, c-Jun, MCL1 and cMYC). In this study, we demonstrate that TRP120 and FBW7 colocalize strongly in the nucleus by confocal immunofluorescent microscopy and interactions between TRP120 and FBW7 FBOX and WD40 domains were demonstrated by ectopic expression and …
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