Search results for "MUTATION"
showing 10 items of 2830 documents
Adjuvant Imatinib in Patients with GIST Harboring Exon 9 KIT Mutations : Results from a Multi-institutional European Retrospective Study
2022
[Purpose] The effect of high-dose imatinib (800 mg/day) on survival in the adjuvant treatment of patients with resected KIT exon 9–mutated gastrointestinal stromal tumors (GIST) is not established. Here, the association of dose and other clinicopathologic variables with survival was evaluated in a large multi-institutional European cohort.
A Multivariate Analysis of HIV-1 Protease Inhibitors and Resistance Induced by Mutation
2005
This paper describes the use of the multivariate statistical procedure principal component analysis as a tool to explore the inhibitory activity of classes of protease inhibitors (PIs) against HIV-1 viruses (wild type and more-frequent single mutants, V82A, V82F, and I84V) and against protease enzymes. The analysis of correlations between biological activity and molecular descriptors or similarity indexes allowed a reliable classification of the 51 derivatives considered in this study. The best results were obtained in the case of the I84V mutant for which a high number of predictions was achieved. On this basis, this statistical approach is proposed as a reliable method for the prediction …
Protein kinase C controls activation of the DNA integrity checkpoint
2014
The protein kinase C (PKC) superfamily plays key regulatory roles in numerous cellular processes. Saccharomyces cerevisiae contains a single PKC, Pkc1, whose main function is cell wall integrity maintenance. In this work, we connect the Pkc1 protein to the maintenance of genome integrity in response to genotoxic stresses. Pkc1 and its kinase activity are necessary for the phosphorylation of checkpoint kinase Rad53, histone H2A and Xrs2 protein after deoxyribonucleic acid (DNA) damage, indicating that Pkc1 is required for activation of checkpoint kinases Mec1 and Tel1. Furthermore, Pkc1 electrophoretic mobility is delayed after inducing DNA damage, which reflects that Pkc1 is post-translatio…
Role of glycine-82 as a pivot point during the transition from the inactive to the active form of the yeast Ras2 protein
1991
AbstractRas proteins bind either GDP or GTP with high affinity. However, only the GTP-bound form of the yeast Ras2 protein is able to stimulate adenylyl cyclase. To identify amino acid residues that play a role in the conversion from the GDP-bound to the GTP-bound state of Ras proteins, we have searched for single amino acid substitutions that selectively affected the binding of one of the two nucleotides. We have found that the replacement of glycine-82 of the Ras2 protein by serine resulted in an increased rate of dissociation of Gpp(NH)p, a nonhydrolysable analog of GTP, while the GDP dissociation rate was not significantly modified. Glycine-82 resides in a region that is highly conserve…
Rot1 plays an antagonistic role to Clb2 in actin cytoskeleton dynamics throughout the cell cycle.
2007
ROT1 is an essential gene whose inactivation causes defects in cell cycle progression and morphogenesis in budding yeast. Rot1 affects the actin cytoskeleton during the cell cycle at two levels. First, it is required for the maintenance of apical growth during bud growth. Second, Rot1 is necessary to polarize actin cytoskeleton to the neck region at the end of mitosis; because of this defect, rot1 cells do not properly form a septum to complete cell division. The inability to polarize the actin cytoskeleton at the end of mitosis is not due to a defect in the recruitment of the polarisome scaffold protein Spa2 or the actin cytoskeleton regulators Cdc42 and Cdc24 in the neck region. Previous …
The MAPK Hog1 recruits Rpd3 histone deacetylase to activate osmoresponsive genes
2003
Regulation of gene expression by mitogen-activated protein kinases (MAPKs) is essential for proper cell adaptation to extracellular stimuli. Exposure of yeast cells to high osmolarity results in rapid activation of the MAPK Hog1, which coordinates the transcriptional programme required for cell survival on osmostress. The mechanisms by which Hog1 and MAPKs in general regulate gene expression are not completely understood, although Hog1 can modify some transcription factors. Here we propose that Hog1 induces gene expression by a mechanism that involves recruiting a specific histone deacetylase complex to the promoters of genes regulated by osmostress. Cells lacking the Rpd3-Sin3 histone deac…
Response of the Saccharomyces cerevisiae Mpk1 Mitogen-Activated Protein Kinase Pathway to Increases in Internal Turgor Pressure Caused by Loss of Ppz…
2004
ABSTRACT The Mpk1 pathway of Saccharomyces cerevisiae is a key determinant of cell wall integrity. A genetic link between the Mpk1 kinase and the Ppz phosphatases has been reported, but the nature of this connection was unclear. Recently, the Ppz phosphatases were shown to be regulators of K + and pH homeostasis. Here, we demonstrate that Ppz-deficient strains display increased steady-state K + levels and sensitivity to increased KCl concentrations. Given these observations and the fact that K + is the major determinant of intracellular turgor pressure, we reasoned that the connection between PPZ1 and - 2 and MPK1 was due to the combination of increased internal turgor pressure in Ppz-defic…
Functional Connection Between the Clb5 Cyclin, the Protein Kinase C Pathway and the Swi4 Transcription Factor in Saccharomyces cerevisiae
2005
Abstract The rsf12 mutation was isolated in a synthetic lethal screen for genes functionally interacting with Swi4. RSF12 is CLB5. The clb5 swi4 mutant cells arrest at G2/M due to the activation of the DNA-damage checkpoint. Defects in DNA integrity was confirmed by the increased rates of chromosome loss and mitotic recombination. Other results suggest the presence of additional defects related to morphogenesis. Interestingly, genes of the PKC pathway rescue the growth defect of clb5 swi4, and pkc1 and slt2 mutations are synthetic lethal with clb5, pointing to a connection between Clb5, the PKC pathway, and Swi4. Different observations suggest that like Clb5, the PKC pathway and Swi4 are in…
Functional distinction between Cln1p and Cln2p cyclins in the control of the Saccharomyces cerevisiae mitotic cycle.
2004
Abstract Cln1p and Cln2p are considered as equivalent cyclins on the basis of sequence homology, regulation, and functional studies. Here we describe a functional distinction between the Cln1p and Cln2p cyclins in the control of the G1/S transition. Inactivation of CLN2, but not of CLN1, leads to a larger-than-normal cell size, whereas overexpression of CLN2, but not of CLN1, results in smaller-than-normal cells. Furthermore, mild ectopic expression of CLN2, but not of CLN1, suppresses the lethality of swi4swi6 and cdc28 mutant strains. In the absence of Cln1p, the kinetics of budding, initiation of DNA replication, and activation of the Start-transcription program are not affected; by cont…
Molecular structure of the cell wall receptor for killer toxin KT28 in Saccharomyces cerevisiae
1988
The adsorption of the yeast killer toxin KT28 to susceptible cells of Saccharomyces cerevisiae was prevented by concanavalin A, which blocks the mannoprotein receptor. Certain mannoprotein mutants of S. cerevisiae that lack definite structures in the mannan of their cell walls were found to be resistant to KT28, whereas the wild-type yeast from which the mutants were derived was susceptible. Isolated mannoprotein from a resistant mutant was unable to adsorb killer toxin. By comparing the resistances of different mannoprotein mutants, information about the molecular structure of the receptor was obtained. At least two mannose residues have to be present in the side chains of the outer chain …