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 94 for “"CDC42"”.
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Opposing Crosstalk between Rho1 and Cdc42 in Epithelial Morphogenesis
… Rho subfamilies have only one member, Rho1 and Cdc42, which allows for straightforward loss-of-function analysis, in vivo. To determine the role of Rho1 and Cdc42 in Drosophila epithelia, we used mosaic clonal analysis and targeted RNA interference expression to perform loss-of-function studies …
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Rational design and optimization of anti-Cdc42 peptide inhibitors
… as inhibitors of the Rho-family GTPase, Cdc42. The research presented builds on previous work which selected Cdc42 binding peptides using CIS-display. The structure of the highest affinity matured peptide (P7) in solution was solved by NMR. A model of the peptide (P7) in complex with …
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Attacking Ras-driven cancers: Engineering a peptide inhibitor for Cdc42
Prior work has indicated that preventing Cdc42 interacting with its downstream effector proteins can reverse Ras-driven oncogenesis. The experiments demonstrating this used the G protein binding region (GBD) of the Cdc42-specific effector ACK, which is 42 amino acids long and binds with 40 nM …
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Spatial Control of CDC42 Activation Regulates Cell Width and Growth Zone Formation
… implicated in the control of the small GTPase Cdc42. Further analyses showed two different pathways are involved: one is defined by the Cdc42 guanine-nucleotide exchange factor (GEF) Scd1 and the second by the GTPase activating protein (GAP) Rga4. Deletions of rga4 and scd1 had additive effects …
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Structural and biochemical insight into the interactions of Cdc42 with TOCA1 and N-WASP
Cdc42 is a member of the Rho family of small GTPases, which, together with its homologues RhoA and Rac1, controls a multitude of cellular functions via the actin cytoskeleton. Cdc42 exerts its effects on the cytoskeleton via effector proteins of the Wiskott-Aldrich Syndrome (WASP) family and the …
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Investigating the Functional Interaction between RhoGDI Family Proteins and Activated Cdc42 associated-kinase (ACK)
… tyrosine kinase and an effector protein for Cdc42. ACK has been implicated in carcinogenesis events especially in promoting cell migration and invasion, indicating a need for a fuller understanding of the cellular roles of ACK both in normal and pathological conditions. A previous …
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The WXXXE Effector Map Functions as a Potent and Specific Guanine Nucleotide Exchange Factor for CDC42
… coli effector Map produces filipodia similar to Cdc42. This study demonstrates that the enzymatic activity of EHEC O157:H7 Map as a specific GEF for cellular Cdc42. Structure/function studies were used to identify key residues and protein regions of Shigella IpgB2, E. coli Map, and Salmonella …
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Αvβ8 Integrin Interacts With Rhogdi1 to Regulate Rac1 and Cdc42 Activation and Drive Glioblastoma Cell Invasion
… to hyperactivation of the Rho GTPases Rac1 and Cdc42. β8 integrin associates with Rho GDP Dissociation Inhibitor 1 (RhoGDI1), an intracellular signaling effector that sequesters Rho GTPases in their inactive GDP-bound states. Silencing RhoGDI1 expression or uncoupling αvβ8 integrin-RhoGDI1 …
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The regulation of the oncogenic STAT transcription factors by the non receptor tyrosine kinase and Cdc42 effector ACK
Activated Cdc42-associated kinase (ACK) is a Rho family effector that is widely implicated in cancer, yet not currently pharmacologically inhibited in the clinic. Through relationships with the androgen receptor in prostate cancer and the oestrogen receptor in breast cancer, ACK regulates …
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Assembly of nuclear dimers of the PI3K regulatory subunits underpins the proliferative activity of Activated Cdc42-associated Kinase, ACK
… nuclear functions that contribute to Cdc42/ACK driven oncogenesis. These dimers represent a previously undescribed mode of regulation for the Class IA PI3K regulatory subunits and potentially reveal additional avenues for therapeutic intervention. The work presented here demonstrates …
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Flourescent Biosensor-Based, Cdc42 Activity Imaging For Understanding the Regulation of Epidermal Growth Receptor (EGFR) Signalling in Head and Neck Cancer
… may stem from aberrant receptor trafficking. Cdc42 is known to affect EGFR downregulation by sequestering c-Cbl, preventing it from catalyzing receptor ubiquitination. The aim of this project is to determine the role of Cdc42 in mediating cancer cell response to EGFR and ErbB-family targeted …
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Reconstitution Of Rho Gtpase Interactions At The Membrane
… between the geranylgeranylated Rho GTPase Cdc42, RhoGDI, and liposomes of well-defined lipid composition. In taking advantage of the sensitivity and real-time capabilities of these reconstituted systems, some unexpected findings emerged regarding how RhoGDI influences the membraneto-cytosol …
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Biochemical and Biophysical Characterization of the Allosteric Equilibrium of the Wiskott-Aldrich Syndrome Protein
… Syndrome protein (WASP) by the Rho-family GTPase Cdc42. Results from this work revealed that a simple two-state model can predict the hydrogen exchange behavior and binding affinity for Cdc42-GTP of WASP proteins over a range of folding stabilities. The goals of my thesis have been: 1) to further …
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Soft 3D fibrin matrices downregulate FAK expression to promote self-renewal of tumor-repopulating cells
… cell division control protein 42 homolog (Cdc42). In comparison to control melanoma cells, TRCs exhibit low FAK and Cdc42 expression. Overexpressing FAK or Cdc42 in TRCs cultured in soft 3D fibrin matrices promotes H3K9 methylation, decreases Sox expression, and suppresses colony growth. …
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Analysis of Growth Cone Signaling During Axon Development in Drosophila Melanogaster
… growth cones expressing constitutively active Cdc42 that displayed guidance defects exhibited little change in their filopodial activity when compared to wild type, whereas others without guidance defects exhibited a significant increase. Moreover, the Y40C effector-loop mutation exerted little …
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Biochemical and Biophysical Studies of Novel Features of Ras-related Protein Interactions
… Ras-related protein Cell division cycle 42 (Cdc42) is important in regulating cell-signaling processes. The T35A mutation in Cdc42 leads to a decrease in flexibility of the Switch I region responsible for effector binding. The kinetics of the intrinsic GTP hydrolysis reaction were compared …
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Systems Biology Analyses of Hematopoietic Cells
… of a signalling pathway in human immune cells. Cdc42 is a membrane associated GTPase that is an important regulator of cytoskeleton rearrangements and is required for natural killer (NK) cell activation. Previous work had shown that Cdc42 activity oscillates during NK immune surveillance after …
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Molecular control of endothelial lumen formation by Rho GTPases in three dimensional collagen matrices
… in vascular morphogenesis. Here, we show that Cdc42 and Rac1 play a key role in endothelial cell (EC) lumen and tube formation in 3D collagen matrices, and that their regulation is mediated by various downstream effectors including Pak2, Pak4, Par3, and Par6b. Both Pak2 and Pak4 phosphorylation …
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