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 19 of 19 for “"PRMT5"”.
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PRMT5 Inhibitors in Merkel Cell Carcinoma
… of protein arginine methyltransferase 5 (PRMT5). PRMT5 inhibitors are already being tested in a variety of other solid and liquid tumors to good effect. Our data suggest that PRMT5 inhibitors may be effective in treating a specific subtype of MCC defined by a viral driver and wildtype p53. …
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Role of Phosphorylation In The Regulation of Prmt5
<p>PRMT5 is a member of a group of proteins that mediate arginine methylation. It is involved in diverse cellular processes, including cell differentiation, splicing, transcription elongation and epigenetic silencing, and its expression is dysregulated in many cancers. Due to its pleiotropic …
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Mechanisms and consequences of resistance to PRMT5 Inhibition
… regulator, protein arginine methyltransferase 5 (PRMT5), is highly expressed in many tumor types and PRMT5 inhibitors are currently in early phase clinical trials. In this dissertation, we have generated the first model of resistance to PRMT5 inhibitors. In Kras-G12D;p53-null lung adenocarcinoma …
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Identification of PRMT5 as a therapeutic target in cholangiocarcinoma
… role of Protein Arginine Methyltransferase 5 (PRMT5) in cholangiocarcinoma, focusing on its functional implications, molecular interactions, and potential as a therapeutic target. Experimental in vitro models were established to evaluate the effects of PRMT5 inhibition on CCA cell proliferation …
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In vivo shRNA screen reveals PRMT5 as a key regulator in glioblastoma
… screens, the protein arginine methyltransferase PRMT5 emerges as an important mediator of GBM tumor growth in the presence and absence of chemotherapy. We demonstrate that PRMT5 loss impairs cellular fitness in vitro and this effect is dependent on its methyltransferase activity. Furthermore, in …
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A Study of The Snd1/Prmt5 Axis In Liver Cancer By Genetic Mouse Models
… in cells. Protein arginine methyltransferase 5 (PRMT5) is the primary enzyme that catalyzes symmetric dimethyl arginine (SDMA) and requires methylosome protein 50 (MEP50) for stability and enzymatic activity which are necessary for life and development. Effector proteins bind different types of …
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Therapeutic Potential of Prmt5 and Mat2A As Synthetic Lethal Targets In Mtap-Deficient Gbm Tumors
… of protein arginine methyltransferase 5 (PRMT5), making these cells sensitive to PRMT5 and MAT2A inhibition. Although elevated levels of MTA <em>in vitro</em> define a promising actionable metabolic vulnerability, the clinical relevance relies on exhibiting significant MTA accumulation in …
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Exploring the role of the arginine-methylation writer-reader pair PRMT5/SND1 in JAK2-mutant myeloproliferative neoplasms
… of Protein Arginine Methyltransferase 5 (PRMT5) has been proposed in JAK2-mutant MPN, highlighting both a mechanism through which this mutation can drive disease progression and a potential mode of therapeutic intervention. Staphylococcal Nuclease Domain-Containing Protein 1 (SND1) is the …
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Targeting PRMT5 impairs cancer proliferation through splicing but promotes state shifts that enable resistance and disease progression
… is protein arginine methyltransferase 5 (PRMT5), which methylates proteins involved in transcription, splicing, and translation. PRMT5 is expressed in a wide variety of tumor types, and preclinical studies show that PRMT5 inhibitors (PRMT5i) effectively suppress cancer cell proliferation. …
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The synthetic dosage lethality between hTERT and DNA damage response associated genes
… initial 5 candidates, genetic assay validated PRMT5 and GNB1L as hTERT SDL partners. The PRMT5-hTERT SDL relationship was then recapitulated via the use of direct PRMT5 protein inhibitors. We also observed that the PRMT5-hTERT SDL relationship influenced the progression of a cell through …
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Crosstalk Between R1175 Methylation and Y1173 Phosphorylation Negatively Modulates Egfr-Mediated Erk Activation
… by a protein arginine methyltransferase named PRMT5. During EGFR activation, PRMT5-mediated R1175 methylation specifically enhances EGF-induced EGFR autophosphorylation at Y1173 residue. This novel modification crosstalk increases SHP1 recruitment to EGFR and suppresses EGFR-mediated ERK …
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The Effects of Methyltransferase Genes on Human Haematopoietic Stem Cell Function
… I have focused on 2 methyltransferase genes, PRMT5 and DNMT3A, which are both epigenetic modulators of HSC function. Pharmacological inhibition of PRMT5 in healthy human cord blood (hCB) haematopoietic stem and progenitor cells (HSPCs) leads to reduced HSPC proliferation and a relative …
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Rational drug combinations to selectively target 9p21-deleted bladder cancer
… loss across several cancer types and identified PRMT5 and MAT2A as synthetic lethal interactions in this context. Consequently, PRMT5 (MRTX1719) and MAT2A (AG270) inhibitors have been developed and are currently being tested in clinical trials to treat MTAP-deleted tumors. Here, we performed a …
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Modulation of the activity of a key metabolic regulator Small Heterodimer Partner by post-translational modifications
… by Protein Arginine Methyltransferase 5 (PRMT5). Functional activity assays showed that methylation of SHP at Arg-57 by PRMT5 is important for SHP inhibition of LRH1 and HNF-4α transactivation. Our lab previously showed the molecular mechanism of SHP-mediated repression involving the …
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Functional characterization of CDY family proteins and their role in recognition of the heterochromatic histone H3K9me3 modification
… von CDYL1 identifiziert werden: PRMT5. PRMT5 ist eine Argininmethyltransferase und in vitro Experimente bestätigen, dass PRMT5 CDYL1 innerhalb des ARKQ Motivs methylieren kann. Das ARKQ Motiv wird auch von der Lysinmethyltransferase G9a modifiziert und benachbarte Serine tragen …
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Investigating the transcription factor landscape of the squamous subtype of pancreatic ductal adenocarcinoma
… targets. Protein Arginine Methyl transferase 5 (PRMT5) shows particular promise as a target, with a panel of squamous cell line models showing significant sensitivity to PRMT5 inhibition in cell-viability and colony formation assays. As the squamous subtype of PDAC is very understudied, this work …
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Semi-Synthesis of the Transcription Factor SMAD2 Containing Caging Groups and Phosphoaminoacid Analogues
… to identify a candidate Smad2-binding protein, PRMT5, that preferentially binds non-phosphorylated Smad2. Studies are ongoing to determine if this interaction has physiological relevance.</p>
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Developing and Using Methyl-Specific Antibodies to Study The Biological Roles of Arginine Methylation
… (GAR or PGM motifs) can also be dimethylated by PRMT5 in a symmetric fashion. However, it is not clear whether there are dedicated residues within these motifs for ADMA and SDMA, or if the two enzyme types (I and II) compete for the same arginine residue. In addition, very little is known about …
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Untersuchungen zur Biogenese spleißosomaler UsnRNPs und ihrer Bedeutung für die Pathogenese der SMA
Die neurodegenerative Krankheit Spinale Muskelatrophie (SMA) wird durch den Mangel an funktionellem Survival Motor Neuron Protein (SMN) verursacht. Eine Funktion von SMN liegt in der Biogenese spleißosomaler UsnRNPs (U-rich small nuclear ribonucleoprotein particles). Diese Arbeit zeigt in einem …