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131.
Pamonsinlapatham P Hadj-Slimane R Raynaud F Bickle M Corneloup C Barthelaix A Lepelletier Y Mercier P Schapira M Samson J Mathieu AL Hugo N Moncorgé O Mikaelian I Dufour S Garbay C Colas P 《PloS one》2008,3(8):e2902
The Ras GTPase-activating protein RasGAP catalyzes the conversion of active GTP-bound Ras into inactive GDP-bound Ras. However, RasGAP also acts as a positive effector of Ras and exerts an anti-apoptotic activity that is independent of its GAP function and that involves its SH3 (Src homology) domain. We used a combinatorial peptide aptamer approach to select a collection of RasGAP SH3 specific ligands. We mapped the peptide aptamer binding sites by performing yeast two-hybrid mating assays against a panel of RasGAP SH3 mutants. We examined the biological activity of a peptide aptamer targeting a pocket delineated by residues D295/7, L313 and W317. This aptamer shows a caspase-independent cytotoxic activity on tumor cell lines. It disrupts the interaction between RasGAP and Aurora B kinase. This work identifies the above-mentioned pocket as an interesting therapeutic target to pursue and points its cognate peptide aptamer as a promising guide to discover RasGAP small-molecule drug candidates. 相似文献
132.
Hakizimana P Masureel M Gbaguidi B Ruysschaert JM Govaerts C 《The Journal of biological chemistry》2008,283(14):9369-9376
In a number of cases, the function of membrane proteins appears to require the presence of specific lipid species in the bilayer. We have shown that the secondary multidrug transporter LmrP requires the presence of phosphatidylethanolamine (PE), as its replacement by phosphatidylcholine (PC) inhibits transport activity and directly affects its structure, although the underlying mechanism was unknown. Here, we show that the effect of PE on the structure and the function of LmrP is mediated by interactions between the lipid headgroup and the protein. We used methyl-PE and dimethyl-PE analogs of PE to show that only replacement of the three hydrogens by methyl moieties leads to changes in the biochemical and biophysical properties of the reconstituted protein. This suggests that LmrP does not depend on the bulk properties of the phospholipids tested but solely on the hydrogen bonding ability of the headgroup. We then show that a single point mutation in LmrP, D68C, is sufficient to recapitulate precisely every biochemical and biophysical effect observed when PE is replaced by PC, including energy transfer between the protein tryptophan residues and the lipid headgroups. We conclude that the negatively charged Asp-68 is likely to participate in the interaction with PE and that such interaction is required for proton gradient sensing, substrate binding, and transport. Because Asp-68 belongs to a highly conserved motif in the Major Facilitator Superfamily (which includes LacY and EmrD), this interaction might be a general feature of these transporters that is involved in proton gradient sensing and lipid dependence. 相似文献
133.
Beck B Lehen'kyi V Roudbaraki M Flourakis M Charveron M Bordat P Polakowska R Prevarskaya N Skryma R 《Cell calcium》2008,43(5):492-505
Aberrant keratinocyte differentiation is considered to be a key mechanism in the onset of hyperproliferative dermatological diseases, including basal cell carcinoma (BCC). It is, therefore, vital to understand what drives keratinocytes to develop such pathological phenotypes. The role of calcium in keratinocyte differentiation is uncontested but the mechanisms controlling calcium-induced differentiation have yet to be completely elucidated. This study was designed to investigate the role of calcium-permeable TRPC channels in human keratinocyte differentiation and BCC, using a combination of molecular and cell biology approaches, involving electrophysiology and Ca(2+)-imaging, on the HaCaT cell line, primary cultures of normal human keratinocytes, and BCC cells. We demonstrated that TRPC1/TRPC4 channel expression was important for keratinocyte differentiation, as knocking out these channels (by siRNA strategy) prevented the induction of Ca(2+)-induced differentiation. TRPC1/TRPC4-mediated calcium entry and endoplasmic reticulum Ca(2+) content increased significantly in differentiated keratinocytes. However, the failure of BCC cells to differentiate was related to a lack of TRPC channel expression and calcium entry. In summary, our data demonstrate that TRPC1 and TRPC4 channels are key elements in keratinocyte Ca(2+) homeostasis and differentiation and may therefore be responsible for skin pathologies. 相似文献
134.
Isabelle Leray Bernard Valeur Dharam Paul Emilie Regnier Matthieu Koepf Jennifer A Wytko Corinne Boudon Jean Weiss 《Photochemical & photobiological sciences》2005,4(3):280-286
Three self-assembled photonic dyads comprising a zinc porphyrin donor and a free base acceptor have been studied by time-resolved fluorescence spectroscopy. The driving force of the assembly is the site selective binding of an imidazole connected to a free base porphyrin. Three spacers have been incorporated between the imidazole connector and the free base porphyrin, providing three different distances separating the donor and the acceptor. The high efficiencies and the rates of energy transfer in the set of dyads is consistent with the Forster energy transfer mechanism. Evidence for Forster back transfer has been obtained, and its efficiency and rate have been quantitatively evaluated for the first time. 相似文献
135.
In this paper a new nanostructured support for the culture of cells is presented. The support consists of fields of sharp
and high-aspect-ratio nanoneedles. The support is obtained through a specifically developed process that allows controlling
the nanoneedles’s densities and height. The nanoneedles are typically 10 μm high with tip diameters under 200 nm. Cell viability
on this support was evaluated through long-term cells cultures. The narrow interface between the cells’ membrane and the nanoneedles
has been carefully observed to conclude on the perforation of the cells’ membrane thanks to the sharp nanoneedles. Such a
nanostructured chip, allowing specific interaction, opens the door to a large number of exciting and valuable applications
such as nanoporation for transfection or internal cell potential recording. 相似文献
136.
Aurélien Sokal Pascal Chappert Giovanna Barba-Spaeth Anais Roeser Slim Fourati Imane Azzaoui Alexis Vandenberghe Ignacio Fernandez Annalisa Meola Magali Bouvier-Alias Etienne Crickx Asma Beldi-Ferchiou Sophie Hue Laetitia Languille Marc Michel Samia Baloul France Noizat-Pirenne Marine Luka Matthieu Mahévas 《Cell》2021,184(5):1201-1213.e14
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137.
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139.
Jean-Marie Matthieu Richard H. Quarles Joseph F. Poduslo Roscoe O. Brady 《Biochimica et Biophysica Acta (BBA)/General Subjects》1975,392(1):159-166
The in vivo incorporation of [3 5S]sulfate and [3H]fucose into rat brain myelin was investigated. Most of the 3 5S in the myelin was in sulfatide, but about 4% was associated with the residual proteins after chloroform/methanol extraction. Polyacrylamide gel electrophoresis of these proteins indicated that the major 3 5S-labeled component corresponded to the major fucose-labeled glycoprotein. The labeling of this predominant glycoprotein with sulfate was more selective than with fucose, since there was relatively little incorporation of sulfate into some of the minor fucose-labeled glycoproteins. There was little or no 3 5S associated with proteolipid or basic protein on polyacrylamide gels. The fucose-labeled glycoproteins were converted to glycopeptides by pronase digestion and separated into two major classes by gel filtration on Sephadex-G50. Only the higher molecular weight class contained significant amounts of 3 5S. The association of 3 5S with the glycopeptides was not due to binding of sulfatide or free inorganic sulfate. The results indicate that the predominant myelin-associated glycoprotein in rat brain is sulfated. 相似文献
140.