25,126 research outputs found
K-Ras Binds Calmodulin-Related Centrin1 with Potential Implications for K-Ras Driven Cancer Cell Stemness
No full textpeer reviewedRecent data suggest that K-Ras4B (hereafter K-Ras) can drive cancer cell stemness via calmodulin (CaM)-dependent, non-canonical Wnt-signalling. Here we examined whether another Ca2+-binding protein, the CaM-related centrin1, binds to K-Ras and could mediate some K-Ras functions that were previously ascribed to CaM. While CaM and centrin1 appear to distinguish between peptides that were derived from their classical targets, they both bind to K-Ras in cells. Cellular BRET- and immunoprecipitation data suggest that CaM engages more with K-Ras than centrin1 and that the interaction with the C-terminal membrane anchor of K-Ras is sufficient for this. Surprisingly, binding of neither K-Ras nor its membrane anchor alone to CaM or centrin1 is sensitive to inhibition of prenylation. In support of an involvement of the G-domain of K-Ras in cellular complexes with these Ca2+-binding proteins, we find that oncogenic K-RasG12V displays increased engagement with both CaM and centrin1. This is abrogated by addition of the D38A effector-site mutation, suggesting that K-RasG12V is held together with CaM or centrin1 in complexes with effectors. When treated with CaM inhibitors, the BRET-interaction of K-RasG12V with centrin1 was also disrupted in the low micromolar range, comparable to that with CaM. While CaM predominates in regulating functional membrane anchorage of K-Ras, it has a very similar co-distribution with centrin1 on mitotic organelles. Given these results, a significant overlap of the CaM- and centrin1-dependent functions of K-Ras is suggested
Daniel Colard. Droit des relations internationales : documents fondamentaux
No full textAbou Diab Khattar. Daniel Colard. Droit des relations internationales : documents fondamentaux. In: Politique étrangère, n°1 - 1989 - 54ᵉannée. p. 141
Drug targeting opportunities en route to Ras nanoclusters.
No full textpeer reviewedDisruption of the native membrane organization of Ras by the farnesyltransferase inhibitor tipifarnib in the late 1990s constituted the first indirect approach to drug target Ras. Since then, our understanding of how dynamically Ras shuttles between subcellular locations has changed significantly. Ras proteins have to arrive at the plasma membrane for efficient MAPK-signal propagation. On the plasma membrane Ras proteins are organized into isoform specific proteo-lipid assemblies called nanocluster. Recent evidence suggests that Ras nanocluster have a specific lipid composition, which supports the recruitment of effectors such as Raf. Conversely, effectors possess lipid-recognition motifs, which appear to serve as co-incidence detectors for the lipid domain of a given Ras isoform. Evidence suggests that dimeric Raf proteins then co-assemble dimeric Ras in an immobile complex, thus forming the minimal unit of an active nanocluster. Here we review established and novel trafficking chaperones and trafficking factors of Ras, along with the set of lipid and protein modulators of Ras nanoclustering. We highlight drug targeting approaches and opportunities against these determinants of functional Ras membrane organization. Finally, we reflect on implications for Ras signaling in polarized cells, such as epithelia, which are a common origin of tumorigenesis
sj-docx-1-ras-10.1177_00208523211065162 - Supplemental material for Conceptualizing talent in public sector municipalities
No full textSupplemental material, sj-docx-1-ras-10.1177_00208523211065162 for Conceptualizing talent in public sector municipalities by Daniel Tyskbo in International Review of Administrative Sciences</p
Promotion of cancer cell stemness by Ras
No full textpeer reviewedCancer stem cells (CSC) may be the most relevant and elusive cancer cell population, as they have the exquisite ability to seed new tumors. It is plausible, that highly mutated cancer genes, such as KRAS, are functionally associated with processes contributing to the emergence of stemness traits. In this review, we will summarize the evidence for a stemness driving activity of oncogenic Ras. This activity appears to differ by Ras isoform, with the highly mutated KRAS having a particularly profound impact. Next to established stemness pathways such as Wnt and Hedgehog (Hh), the precise, cell cycle dependent orchestration of the MAPK-pathway appears to relay Ras activation in this context. We will examine how non-canonical activities of K-Ras4B (hereafter K-Ras) could be enabled by its trafficking chaperones calmodulin and PDE6D/PDEδ. Both dynamically localize to the cellular machinery that is intimately linked to cell fate decisions, such as the primary cilium and the centrosome. Thus, it can be speculated that oncogenic K-Ras disrupts fundamental polarized signaling and asymmetric apportioning processes that are necessary during cell differentiation
Les parties à l'instance d'appel en matière civile.Thèse de doctorat d'État (Rennes 1980). Youssef ABOU-ZEID
No full textCosnard Henri-Daniel. Les parties à l'instance d'appel en matière civile.Thèse de doctorat d'État (Rennes 1980). Youssef ABOU-ZEID. In: Revue Judiciaire de l'Ouest, 1980-2. pp. 134-135
sj-docx-1-ras-10.1177_00208523231159244 - Supplemental material for Factors influencing political corruption. An empirical research study of regional governments
No full textSupplemental material, sj-docx-1-ras-10.1177_00208523231159244 for Factors influencing political corruption. An empirical research study of regional governments by Daniel Raya-Quero, Andrés Navarro-Galera and José Luis Sáez-Lozano in International Review of Administrative Sciences</p
Characterization of Grain Boundaries in Cu(In,Ga)Se Films Using Atom-Probe Tomography
No full textThis paper discusses the advantages of pulsed laser atom-probe tomography (APT) to analyze Cu(In,Ga)Se-2-based solar cells. Electron backscatter diffraction (EBSD) was exploited for site-specific preparation of APT samples at selected Cu(In,Ga)Se-2 grain boundaries. This approach is very helpful not only to determine the location of grain boundaries but also to classify them as well. We demonstrate that correlative transmission electron microscopy (TEM) analyses on atom-probe specimens enable the atom-probe datasets to be reconstructed with high accuracy. Moreover, EBSD and TEM can be very useful to obtain complementary information about the crystal structure in addition to the compositional analyses. The local chemical compositions at grain boundaries of a solar grade Cu(In,Ga)Se-2 film are presented here. Na, K, and O impurities are found to be segregated at grain boundaries. These impurities most likely diffuse from the soda lime glass substrate into the absorber layer during cell fabrication and processing. Based on the experimental results, we propose that Na, K, and O play an important role in the electrical properties of grain boundaries in Cu(In,Ga)Se-2 thin films for solar cell
The role of the CDP-choline pathway in the anoikis resitance of Ras transformed intestinal epithelial cells
No full textPhosphatidylcholine (PC) is an essential component of biological membranes and is synthesized by the CDP-choline pathway under the control of the rate-limiting enzyme CTP:phosphocholine cytidylyltransferase-alpha (CCT?). Ras transformed cells have increased lipid synthesis; the aim of this study was to determine if upregulation of CCT? was part of this transformed phenotype. Rat intestinal epithelial cell lines (IEC) and three oncogenic H-ras expressing IEC (IEC-Ras) were used to investigate the role of CCT? and phosphatidylcholine (PC) synthesis in resistance to detachment dependant apoptosis, termed anoikis. IEC-Ras have increased CCT? expression within the nucleus. Reduction of CCT? expression with lentiviral short hairpin RNA sensitized IEC-Ras to anoikis and decreased PC degradation, but did not change PC synthesis. Thus, in addition to CCT? being involved in anoikis-resistance in IEC-Ras these data indicate the possibility that it may also have nuclear-specific functions
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