mg-262 has been researched along with epoxomicin* in 2 studies
2 other study(ies) available for mg-262 and epoxomicin
Article | Year |
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A transgenic mouse model of the ubiquitin/proteasome system.
Impairment of the ubiquitin/proteasome system has been proposed to play a role in neurodegenerative disorders such as Alzheimer and Parkinson diseases. Although recent studies confirmed that some disease-related proteins block proteasomal degradation, and despite the existence of excellent animal models of both diseases, in vivo data about the system are lacking. We have developed a model for in vivo analysis of the ubiquitin/proteasome system by generating mouse strains transgenic for a green fluorescent protein (GFP) reporter carrying a constitutively active degradation signal. Administration of proteasome inhibitors to the transgenic animals resulted in a substantial accumulation of GFP in multiple tissues, confirming the in vivo functionality of the reporter. Moreover, accumulation of the reporter was induced in primary neurons by UBB+1, an aberrant ubiquitin found in Alzheimer disease. These transgenic animals provide a tool for monitoring the status of the ubiquitin/proteasome system in physiologic or pathologic conditions. Topics: Alzheimer Disease; Animals; Boronic Acids; Cells, Cultured; Cysteine Endopeptidases; Fibroblasts; Leupeptins; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microscopy, Fluorescence; Models, Animal; Multienzyme Complexes; Myocytes, Cardiac; Neurodegenerative Diseases; Neurons; Oligopeptides; Organ Specificity; Parkinson Disease; Proteasome Endopeptidase Complex; Recombinant Fusion Proteins; Tissue Distribution; Ubiquitin | 2003 |
Cells adapted to the proteasome inhibitor 4-hydroxy- 5-iodo-3-nitrophenylacetyl-Leu-Leu-leucinal-vinyl sulfone require enzymatically active proteasomes for continued survival.
The proteasome is the primary protease used by cells for degrading proteins and generating peptide ligands for class I molecules of the major histocompatibility complex. Based on the properties of cells adapted to grow in the presence of the proteasome inhibitor 4-hydroxy-5-iodo-3-nitrophenylacetyl-Leu-Leu-leucinal-vinyl sulfone (NLVS), it was proposed that proteasomes can be replaced by alternative proteolytic systems, particularly a large proteolytic complex with a tripeptidyl peptidase II activity. Here we show that NLVS-adapted cells retain sensitivity to a number of highly specific proteasome inhibitors with regard to antigenic peptide generation, accumulation of polyubiquitinated proteins, degradation of p53, and cell viability. In addition, we show that in the same assays (with a single minor exception), NLVS-adapted cells are about as sensitive as nonselected cells to Ala-Ala-Phe-chloromethylketone, a specific inhibitor of tripeptidyl peptidase II activity. Based on these findings, we conclude that proteasomes still have essential proteolytic functions in adapted cells that are not replaced by Ala-Ala-Phe-chloromethylketone-sensitive proteases. Topics: Amino Acid Chloromethyl Ketones; Aminopeptidases; Animals; Antigen Presentation; Antigens; Boronic Acids; Bortezomib; CD8-Positive T-Lymphocytes; Cell Survival; Cysteine Endopeptidases; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; Drug Resistance; Endopeptidases; Enzyme Activation; H-2 Antigens; Leupeptins; Lymphoma, T-Cell; Mice; Multienzyme Complexes; Neoplasm Proteins; Oligopeptides; Peptide Fragments; Phenols; Protease Inhibitors; Proteasome Endopeptidase Complex; Protein Processing, Post-Translational; Pyrazines; Selection, Genetic; Serine Endopeptidases; Sulfones; Thymus Neoplasms; Tumor Cells, Cultured; Tumor Suppressor Protein p53; Tyramine; Ubiquitins | 2001 |