Search results for "protein degradation"

Abstract 1690: Differential autophagy activation in KRAS and EGFR mutant lung adenocarcinomas.

2013

Abstract Lung cancer is the leading cause of cancer deaths in western countries, and adenocarcinomas (LADs) are the most frequent histological subtype. The aberrant activation of the kinases promotes plethora of tumorigenic processes, mainly through PI3K and MAPK oncogenic pathways leading to oncogene addiction. The activation of PI3K pathway deregulates mTOR, a master kinase for cell growth and autophagy. Autophagy can be pro- or anti- tumorigenic, however its roles in protecting tumors exposed to metabolic stress under chemotherapy are considered as a survival mechanism for the tumors leading to acquired resistance. Consequently, the inhibition of autophagy is an attractive therapy to pre…

Effects of vinblastine, leucine, and histidine, and 3-methyladenine on autophagy in Ehrlich ascites cells.

1990

The microtubule inhibitor vinblastine causes accumulation of autophagic vacuoles in many cell types. In hepatocytes, many of the accumulated vacuoles are nascent, which has been interpreted to suggest that vinblastine acts by inhibiting the fusion of hydrolase-containing lysosomes with early autophagic vacuoles. However, our previous results suggested that, in Ehrlich ascites cells, vinblastine causes accumulation mainly of older autophagic vacuoles (AVs). This study was undertaken to further characterize the mode of action of vinblastine in these cells. The vinblastine-accumulated AVs were quantified by electron-microscopic morphometry. In addition, the effects of inhibitors of autophagic …

Molecular evidence for the inverse comorbidity between central nervous system disorders and cancers detected by transcriptomic meta-analyses.

2014

There is epidemiological evidence that patients with certain Central Nervous System (CNS) disorders have a lower than expected probability of developing some types of Cancer. We tested here the hypothesis that this inverse comorbidity is driven by molecular processes common to CNS disorders and Cancers, and that are deregulated in opposite directions. We conducted transcriptomic meta-analyses of three CNS disorders (Alzheimer's disease, Parkinson's disease and Schizophrenia) and three Cancer types (Lung, Prostate, Colorectal) previously described with inverse comorbidities. A significant overlap was observed between the genes upregulated in CNS disorders and downregulated in Cancers, as wel…

Transcriptome profiling of citrus fruit response to huanglongbing disease.

2010

Huanglongbing (HLB) or "citrus greening" is the most destructive citrus disease worldwide. In this work, we studied host responses of citrus to infection with Candidatus Liberibacter asiaticus (CaLas) using next-generation sequencing technologies. A deep mRNA profile was obtained from peel of healthy and HLB- affected fruit. It was followed by pathway and protein-protein network analysis and quantitative real time PCR analysis of highly regulated genes. We identified differentially regulated pathways and constructed networks that provide a deep insight into the metabolism of affected fruit. Data mining revealed that HLB enhanced transcription of genes involved in the light reactions of phot…

Acidic cytosolic proteins are preferentially imported into rat liver lysosomes.

1998

Previous studies have reported that lysosomes isolated from human diploid fibroblasts and from rat liver can selectively import and degrade specific proteins. We have now reinvestigated this selectivity using an in vitro assay with rat liver lysosomes and an extract of cytosolic proteins prepared from cultured cells labeled to equilibriums with [35S-]methionine. Analysis by two-dimensional gel electrophoresis and autoradiography of the cytosolic proteins bound to the lysosomal membrane and imported into the lysosomes shows that when all cytosolic proteins are simultaneously present in the in vitro assay the lysosomal uptake also occurs in a specific manner. These findings suggest that isola…

2020

Skeletal muscle atrophy is characterized by a decrease in muscle fiber size as a result of a decreased protein synthesis, which leads to degradation of contractile muscle fibers. It can occur after denervation and immobilization, and glucocorticoids (GCs) may also increase protein breakdown contributing to the loss of muscle mass and myofibrillar proteins. GCs are already used in vitro to induce atrophic conditions, but until now no studies with primary human skeletal muscle existed. Therefore, this study deals with the effects of the GC dexamethasone (dex) on primary human myoblasts and myotubes. After incubation with 1, 10, and 100 µM dex for 48 and 72 h, gene and protein expression analy…

Midregion PTHrP and Human Breast Cancer Cells

2010

PTHrP is a polyhormone undergoing proteolytic processing into smaller bioactive forms, comprising an N-terminal peptide, which is the mediator of the “classical” PTH-like effect, as well as midregion and C-terminal peptides. The midregion PTHrP domain (38-94)-amide was found to restrain growth and invasionin vitroof some breast cancer cell lines, causing striking toxicity and accelerating death; the most responsive being MDA-MB231, whose tumorigenesis was also attenuatedin vivo. In addition, midregion PTHrP appears to be imported in the nucleoplasm of cultured MDA-MB231 cells andin vitro, it can bind chromatin of metaphase spread preparations and also an isolated 20-mer oligonucleotide, the…

Oxidative stress tolerance, adenylate cyclase, and autophagy are key players in the chronological life span of Saccharomyces cerevisiae during winema…

2012

Most grape juice fermentation takes place when yeast cells are in a nondividing state called the stationary phase. Under such circumstances, we aimed to identify the genetic determinants controlling longevity, known as the chronological life span. We identified commercial strains with both short (EC1118) and long (CSM) life spans in laboratory growth medium and compared them under diverse conditions. Strain CSM shows better tolerance to stresses, including oxidative stress, in the stationary phase. This is reflected during winemaking, when this strain has an increased maximum life span. Compared to EC1118, CSM overexpresses a mitochondrial rhodanese gene-like gene, RDL2, whose deletion lead…

Yeast Dun1 Kinase Regulates Ribonucleotide Reductase Inhibitor Sml1 in Response to Iron Deficiency

2014

Iron is an essential micronutrient for all eukaryotic organisms because it participates as a redox-active cofactor in many biological processes, including DNA replication and repair. Eukaryotic ribonucleotide reductases (RNRs) are Fe-dependent enzymes that catalyze deoxyribonucleoside diphosphate (dNDP) synthesis. We show here that the levels of the Sml1 protein, a yeast RNR large-subunit inhibitor, specifically decrease in response to both nutritional and genetic Fe deficiencies in a Dun1-dependent but Mec1/Rad53- and Aft1-independent manner. The decline of Sml1 protein levels upon Fe starvation depends on Dun1 forkhead-associated and kinase domains, the 26S proteasome, and the vacuolar pr…

Selective uptake and degradation of c-Fos and v-Fos by rat liver lysosomes

1996

AbstractThe transcription factor c-Fos is a short-lived protein and calpains and ubiquitin-dependent systems have been proposed to be involved in its degradation. In this report, we consider a lysosomal degradation pathway for c-Fos. Using a cell-free assay, we have found that freshly isolated lysosomes can take up and degrade c-Fos with high efficiency. v-Fos, the oncogenic counterpart of c-Fos, can also be taken up by lysosomes, yet the amount of incorporated protein is much lower. c-Fos uptake is independent of its phosphorylation state but it appears to be regulated by dimerization with differentially phosphorylated forms of c-Jun, while v-Fos escapes this regulation. Moreover, we show …