Search results for "ubiquitination"
showing 10 items of 39 documents
Rapid inactivation and proteasome-mediated degradation of OGG1 contribute to the synergistic effect of hyperthermia on genotoxic treatments
2013
Inhibition of DNA repair has been proposed as a mechanism underlying heat-induced sensitization of tumour cells to some anticancer treatments. Base excision repair (BER) constitutes the main pathway for the repair of DNA lesions induced by oxidizing or alkylating agents. Here, we report that mild hyperthermia, without toxic consequences per se, affects cellular DNA glycosylase activities, thus impairing BER. Exposure of cells to mild hyperthermia leads to a rapid and selective inactivation of OGG1 (8-oxoguanine DNA glycosylase) associated with the relocalisation of the protein into a detergent-resistant cellular fraction. Following its inactivation, OGG1 is ubiquitinated and directed to pro…
HSP27 controls GATA-1 protein level during erythroid cell differentiation.
2010
AbstractHeat shock protein 27 (HSP27) is a chaperone whose cellular expression increases in response to various stresses and protects the cell either by inhibiting apoptotic cell death or by promoting the ubiquitination and proteasomal degradation of specific proteins. Here, we show that globin transcription factor 1 (GATA-1) is a client protein of HSP27. In 2 models of erythroid differentiation; that is, in the human erythroleukemia cell line, K562 induced to differentiate into erythroid cells on hemin exposure and CD34+ human cells ex vivo driven to erythroid differentiation in liquid culture, depletion of HSP27 provokes an accumulation of GATA-1 and impairs terminal maturation. More spec…
The K63 deubiquitinase CYLD modulates autism-like behaviors and hippocampal plasticity by regulating autophagy and mTOR signaling.
2021
Nondegradative ubiquitin chains attached to specific targets via Lysine 63 (K63) residues have emerged to play a fundamental role in synaptic function. The K63-specific deubiquitinase CYLD has been widely studied in immune cells and lately also in neurons. To better understand if CYLD plays a role in brain and synapse homeostasis, we analyzed the behavioral profile of CYLD-deficient mice. We found that the loss of CYLD results in major autism-like phenotypes including impaired social communication, increased repetitive behavior, and cognitive dysfunction. Furthermore, the absence of CYLD leads to a reduction in hippocampal network excitability, long-term potentiation, and pyramidal neuron s…
A protein quality control pathway regulated by linear ubiquitination.
2019
Neurodegenerative diseases are characterized by the accumulation of misfolded proteins in the brain. Insights into protein quality control mechanisms to prevent neuronal dysfunction and cell death are crucial in developing causal therapies. Here, we report that various disease-associated protein aggregates are modified by the linear ubiquitin chain assembly complex (LUBAC). HOIP, the catalytic component of LUBAC, is recruited to misfolded Huntingtin in a p97/VCP-dependent manner, resulting in the assembly of linear polyubiquitin. As a consequence, the interactive surface of misfolded Huntingtin species is shielded from unwanted interactions, for example with the low complexity sequence doma…
Altered REDD1, myostatin, and Akt/mTOR/FoxO/MAPK signaling in streptozotocin-induced diabetic muscle atrophy
2011
Type 1 diabetes, if poorly controlled, leads to skeletal muscle atrophy, decreasing the quality of life. We aimed to search highly responsive genes in diabetic muscle atrophy in a common diabetes model and to further characterize associated signaling pathways. Mice were killed 1, 3, or 5 wk after streptozotocin or control. Gene expression of calf muscles was analyzed using microarray and protein signaling with Western blotting. We identified translational repressor protein REDD1 (regulated in development and DNA damage responses) that increased seven- to eightfold and was associated with muscle atrophy in diabetes. The diabetes-induced increase in REDD1 was confirmed at the protein level. …
Heat Shock Proteins: Cell Protection through Protein Triage
2010
Heat shock proteins (HSPs) are chaperones that catalyze the proper folding of nascent proteins and the refolding of denatured proteins. The ubiquitin-proteasome system is an error-checking system that directs improperly folded proteins for destruction. A coordinated interaction between the HSPs (renaturation) and the proteasome (degradation) must exist to assure protein quality control mechanisms. Although it still remains unknown how the decision of folding vs. degradation is taken, many pieces of evidence demonstrate that HSPs interact directly or indirectly with the proteasome, assuring quite selectively the proteasomal degradation of certain proteins under stress conditions. In this rev…
Curcumin Affects HSP60 Folding Activity and Levels in Neuroblastoma Cells.
2020
The fundamental challenge in fighting cancer is the development of protective agents able to interfere with the classical pathways of malignant transformation, such as extracellular matrix remodeling, epithelial−mesenchymal transition and, alteration of protein homeostasis. In the tumors of the brain, proteotoxic stress represents one of the main triggering agents for cell transformation. Curcumin is a natural compound with anti-inflammatory and anti-cancer properties with promising potential for the development of therapeutic drugs for the treatment of cancer as well as neurodegenerative diseases. Among the mediators of cancer development, HSP60 is a key factor for the maintenance of…
Theileria parasites secrete a prolyl isomerase to maintain host leukocyte transformation
2015
Infectious agents develop intricate mechanisms to interact with host cell pathways and hijack their genetic and epigenetic machinery to change host cell phenotypic states. Among the Apicomplexa phylum of obligate intracellular parasites, which cause veterinary and human diseases, Theileria is the only genus that transforms its mammalian host cells. Theileria infection of bovine leukocytes induces proliferative and invasive phenotypes associated with activated signalling pathways, notably JNK and AP-1 (ref. 2). The transformed phenotypes are reversed by treatment with the theilericidal drug buparvaquone. We used comparative genomics to identify a homologue of the peptidyl-prolyl isomerase PI…
Unveiling novel interactions of histone chaperone Asf1 linked to TREX-2 factors Sus1 and Thp1
2014
13 páginas, 7 figuras, 2 yablas
Ubiquitin ligase Rsp5p is involved in the gene expression changes during nutrient limitation inSaccharomyces cerevisiae
2009
Rsp5p is an essential ubiquitin ligase involved in many different cellular events, including amino acid transporters degradation, transcription initiation and mRNA export. It plays important role in both stress resistance and adaptation to the change of nutrients. We have found that ubiquitination machinery is necessary for the correct induction of the stress response SPI1 gene at the entry of the stationary phase. SPI1 is a gene whose expression is regulated by the nutritional status of the cell and whose deletion causes hypersensitivity to various stresses, such as heat shock, alkaline stress and oxidative stress. Its regulation is mastered by Rsp5p, as mutations in this gene lead to a lo…