50 results about "Deubiquitination" patented technology

The invention provides the application of IU1 in the preparation of a drug for treating p53-deficient tumors, and belongs to the technical field of tumor drugs. The application of IU1 having the structure shown in formula I in the preparation of a medicament for treating p53-deficient tumors. Specific inhibition of the deubiquitinase USP14 with the small-molecule inhibitor IU1 resulted in persistent tumor regression of lymphomas and sarcomas in p53-deficient mice without affecting normal tissues, and treatment response was associated with increased COPS5 ubiquitination. IU1-specific inhibition of USP14 resulted in durable tumor regression through a mechanism of COPS5 deubiquitination and p53-dependent and independent regulation of USP14.

The invention relates to a lysine site mutant of conjugated ubiquitin of mda-7 / IL-24 and application thereof, belonging to the field of genetic engineering. In the invention, lysine codons of 63rd, 69th, 78th, 119th, 123rd, 136th, 179th, 189th, 203rd and 206th potential conjugated ubiquitin sites of the mda-7 / IL-24 are mutated into arginine codons by utilizing a site-directed mutation PCR (Polymerase Chain Reaction) technology and cloned to pcDNA3.1(+) plasmids; after the mutant plasmids are transfected with cervical carcinoma Hela cells and hepatoma carcinoma HepG2 cells, the expressions of mda-7 / IL-24 protein and ubiquitination mda-7 / IL-24 protein are respectively detected. A result shows that the quantity of the mda-7 / IL-24 protein expressed by a 123rd lysine mutant of the mda-7 / IL-24 is remarkably increased, and the quantity of the ubiquitination mda-7 / IL-24 protein is remarkably decreased. The invention proves that the 123rd lysine of the mda-7 / IL-24 is an ubiquitination site, and mda-7 / IL-24 mutants generated by the mutant plasmids are difficult to be degraded by the in-vivo ubiquitin, thereby enhancing the expression and the action of the mda-7 / IL-24 in tumour cells.

The present invention relates to a method for treatment or prevention of a hemorrhagic condition in a patient by administering plasminogen activator inhibitor-1 (“PAI-1”) and / or an inhibitor of deubiquitinating enzyme CYLD (“CYLD”) to a patient. Pharmaceutical compositions that include one or both of PAI-1 and an inhibitor of CYLD are also disclosed.

The invention relates to the field of biology and medicine and discloses an application of holomycin in inhibition of the activation of an NLRP3 inflammasome. The holomycin can inhibit NLRP3 protein self-deubiquitination under agonist stimulation, binding of NLRP3 to an ASC protein, formation of ASC spots and activation of Caspase-1, and finally inhibit IL-1 beta and IL-18 secretion. The holomycincan inhibit monosodium urate-induced peritonitis in vivo. Therefore, holomycin can be used a specific drug for treatment on NLRP3 abnormal activation-related diseases.

The invention provides the use of USP33 as a drug target in the preparation of medicines, belonging to the field of protein engineering. The present invention utilizes co-immunoprecipitation and mass spectrometry techniques to discover the deubiquitinating enzyme USP33 that interacts with Parkin, and further discovers that USP33 is located in the mitochondrial outer membrane and can deubiquitinate and modify the E3 ligase Parkin. Knockdown of USP33 will promote the translocation of Parkin to mitochondria, thereby enhancing mitophagy to remove damaged mitochondria, confirming that USP33 regulates mitophagy by affecting the deubiquitination of Parkin, and knocking down USP33 can inhibit the expression of neurons under MPTP treatment. Apoptosis, USP33 can be used as a drug target to prepare drugs, and has good application potential and value.