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.
Results
Showing 1 to 20 of 32 for “"BRD4"”.
-
Multiple Functions of BRD4 in E2 Mediated HPV Transciptional Regulation
… we identified bromodomain-containing protein 4 (Brd4) as a cellular corepressor for E2-mediated inhibition of HPV transcription. Brd4 contains two bromodomains which function as acetyl-lysine-binding modules that facilitate chromatin targeting via their interactions with acetylated histones. …
-
The role of BRD4 in the innate immune response to gastrointestinal infection
Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2025-08-01
-
Epigenetic regulation of gene expression by BRD4 in cancer and innate immune response
… cancers. The bromodomain-containing protein 4 (BRD4), one of the BET (bromodomain and extra terminal) family proteins, represents a class of epigenetic readers that regulate gene transcription by binding to acetylated lysine of histone and non-histone proteins via their bromodomains (BDs). This …
-
A CORRELATIVE CRYO-ELECTRON TOMOGRAPHY APPROACH TO STUDY BRD4-NUT CHROMATIN CONDENSATES ACROSS SCALES
… NUT carcinoma, in which the fusion oncoprotein BRD4-NUT leads to aberrant chromosomal megadomains with liquid-like behavior. While biochemical and genomic studies have investigated the condensation mechanisms and molecular functions of these BMCs, their architecture remains substantially …
-
Studies of the Molecular Features of Brd4-Nut and P300 That Contribute to Condensate Formation and Transcriptional Regulation
… in several cancers. The oncogenic fusion protein Brd4-Nut drives aberrant gene expression and forms condensates in Nut Carcinoma (NC). It has not been clear how these condensates form and whether they modulate gene expression. Here, I dissected the molecular features of Brd4-Nut and a histone …
-
Modulation of Host BRD4 to Repress HIV Replication in Myeloid Cells: Major HIV Reservoirs in Central Nervous System
… are needed. Our group has recently identified a BRD4-selective small molecule modulator (ZL0580) that induces epigenetic suppression of HIV. Here, we examined the effects of this compound on HIV in human myeloid cells. We found that ZL0580 induces potent and durable suppression of both induced …
-
The role of BET proteins in castration-resistant prostate cancer dissemination
… and ExtraTerminal (BET – BRD2, BRD3 and BRD4) family of proteins, to test the hypothesis that each BET family member regulates EMT and underlying characteristics such as cell motility and invasiveness. We systematically manipulated the BET proteins and found that BRD4 regulates cell …
-
Mechanistic and Therapeutic Insights for Epigenetic Regulation in Cancer Development
… of chromatin regulator/BET bromodomain protein BRD4, and paradoxically, sensitivity and resistance to BET bromodomain inhibition with small molecule inhibitor JQ1. Indeed, genetic and pharmacological inhibition of BRD4 profoundly suppresses both growth and tumorigenesis of MPNSTs. …
-
Development of SiRNA Incorporated Surface Modified Polymeric Nanoparticle for the Potential Treatment of Global Cerebral Ischemia
… function. Bromodomain-containing protein 4 (BRD4) plays a pivotal role in the transcriptional regulation of inflammation in this event. Therefore, inhibiting BRD4 may be a novel therapeutic strategy for decreasing neuroinflammation and delaying cognitive deficits. RNAi technology has the …
-
Development of Protein Degraders Inspired by Chemical Modifications
… a Dha-based bromodomain-containing protein 4 (BRD4) degrader was synthesized and demonstrated to induce consistent attenuation of BRD4 levels at micromolar potency. Subsequent optimization revealed that a spacer is not required for Dha-based degrader design, indicating that Dha itself can …
-
Molecular regulation of BRD3 in forward programming of Megakaryocytes
… of platelet traits. BRD3, along with BRD2, BRD4 and BRDT, is classified within the bromodomain and extra terminal (BET) family, specialised in recognising and binding to acetylated lysine residues. In this project, I studied the functions of BRD3 during megakaryopoiesis, the process that …
-
Identifying Molecular Targets and Validating Novel Therapies For Ovarian Cancer
… (BETis), which target proteins such as BRD4, held the greatest promise to produce therapeutic effects and impact relevant oncogenic gene targets, such as Notch3,<strong> </strong>in this disease. In our pre-clinical models, we demonstrated that BETis produce therapeutic effects and …
-
H2A.Z : a molecular rheostat for gene regulation in embryonic stem cells
… siRNA inhibition of another BET family member Brd4, does not restore repression suggesting that Brd2 and Brd4 play distinct roles in ESCs. This thesis provides novel insights into how H2A.Z acts as a molecular rheostat to regulate the balance between active and silent genes in ESCs, and more …
-
Polyphosphate Modification of Human Proteins and a New Mechanism for Regulating Super-Enhancer Activity
… the Mediator subunit MED1, the coactivator BRD4, and the transcription factor YY1. These modifications disrupted their capacity for phase separation, reduced MED1 and BRD4 expression and impaired YY1 nuclear localization. In addition, polyP inhibited YY1 dimer formation and disrupted …
-
Small-molecule inhibition of general transcriptional regulators in cancer
… regulators - the CDK7-inhibitor THZ1 and the BRD4-inhibitor JQ1 - and suggest a model describing the molecular basis of the synergistic effects I observed. My research provides insight into the effects of these inhibitors of general transcriptional regulators on tumor cell behavior and gene …
-
Fibroblasts: Key Cells in Inflammation and Fibrosis
… elongation of target genes suggests that both BRD4 (bromodomain and ET domain containing protein 4) and CDK9 (cyclin dependent kinase 9) are needed for myofibroblast transformation. I further identify a small molecule inhibitor of BRD4, JQ1, which can not only prevent but also reverse the …
-
The Cell-Essentiality of KAT7 in Acute Myeloid Leukemia
… MLL-fusion associated adaptor proteins such as BRD4 and AF4 to gene promoters, which are critical for the maintenance of the MLL-AF9 transcriptional programme. Although not found to be mutated among cases of AML, KAT7 is a plausible therapeutic target for this poor prognosis subtype of AML.
-
Part I: Steroid Receptor CO-Activator 3 (SRC-3) Expression in Lung Cancer and its Role in Regulating Cancer Cell Survival and Proliferation; Part II: Development of Phosphospecific Peptoid Ligand
… to a serine-phosphorylated PDID domain of Brd4 protein, identified by screening a library of 40,000 peptoids for PDID binders. The isolated hit peptoids are only specific to phos-PDID, but not the non-phosphorylated form of the protein, or other phosphoserine- or phosphothreonine-containing …
-
Designed bifunctional proteins for induced degradation of androgen receptor in prostate cancer
… The most promising results were obtained for the BRD4-BD1 domain onto which the NRF2 peptide was grafted to bind to KEAP1. The designed BRD4-NRF2 pulled down AR in cells, but unexpectedly revealed low binding affinity using biophysical methods. The identification of suitable AR binders was …
Page 1 of 2