49 results about "Ubiquitinated Proteins" patented technology

The invention relates to particular ubiquitination epitopes, antibodies that specifically recognize and bind to ubiquitinated proteins and peptides (particularly after the ubiquitin is removed by proteolytic cleavage) and to methods of using these epitopes and antibodies.

We describe a bis-benzylidine piperidone, RA190, which covalently binds to the ubiquitin receptor RPN13 (ADRM1) in the 19S regulatory particle and inhibits proteasome function, triggering rapid accumulation of polyubiquitinated proteins. Multiple myeloma lines, even those resistant to bortezomib, were sensitive to RA190 via ER stress-related apoptosis. RA190 stabilized targets of human papillomavirus (HPV) E6 oncoprotein, and preferentially killed HPV-transformed cells. After p.o. or i.p. dosing of mice, RA190 distributed to plasma and major organs excepting brain, and potently inhibited proteasome function in skin and muscle. RA190 administration i.p. profoundly reduced growth of multiple myeloma and ovarian cancer xenografts, and oral RA190 treatment retarded HPV+ syngeneic mouse tumor growth, without impacting spontaneous HPV-specific CD8+ T cell responses, suggesting its therapeutic potential. The bis-benzylidine piperidone RA190 is a new orally-available proteasome inhibitor. Multiple myeloma, cervical and ovarian cancers are particularly sensitive to RA190.

The present invention relates to methods and compositions for identifying covalent joining or modification of proteins. In particular, the present invention relates to covalent fluorescence complementation assays for the detection of modified (e.g., ubiquitinated proteins). The present invention further relates to the use of such fluorescence complementation assays in drug screening and research applications.

There is provided antibodies, epitopes and methods for detecting ubiquitinated polypeptides and ubiquitination sites in proteins. The antibodies recognize a fragment of ubiquitin that is created after samples are treated with the proteoloytical enzyme LysC (or LysN).

The invention discloses anti-tumor ubiquitinated protein which is mainly extracted from the following steps: (1) culture of tumor cells: resuscitating cryopreserved tumor cells and culturing the tumor cells according to a conventional culture method; (2) treatment of the tumor cells; and (3) extraction of the ubiquitinated protein. The invention further discloses an extraction method of the anti-tumor ubiquitinated protein as well as application of the anti-tumor ubiquitinated protein in preparing tumor therapeutic vaccines. Compared to the prior art, the protein disclosed by the invention can be used for greatly improving the effect of cross-immuno reaction and improving the inhibitory effect on different types of tumors to a great extent; in addition, the problem that ubiquitinated short-lived protein is fast to degrade is further overcome, and a lot of ubiquitinated protein can be quickly obtained. Finally, the asymmetry between the short-lived protein and the long-lived protein is overcome, the target spots for inducing specific effector cells are increased, and the defect that the anti-tumor vaccines are poor in anti-tumor effect based on the long-lived protein is remedied.

Viruses having an impaired ability to deISGylate ISG15 conjugates, in particular, viral mutants comprising a mutation in the viral genome that reduces or eliminates the ability of the viral OTU domain-containing protein encoded by the viral genome to deISGylate ISG15 conjugates and/or deubiquitinate ubiquitinated proteins and/or deNeddylate Neddylated proteins are disclosed. Such viral mutants may be used in the formulation of immunogenic compositions for inducing an immune response and preventing, managing and/or treating a viral infection. Also disclosed are methods for identifying anti-viral compounds, in particular, methods of identifying compounds that reduce or inhibit the deISGylation activity and/or deubiquitination and/or deNeddylation activity of a viral OTU domain-containing protein. The compounds identified using such methods may be used as antiviral agents for the prevention, treatment and/or management of viral infections.

Disclosed are small molecule inhibitors of deubiquitinating enzymes (DUBs), and methods of using them. Certain compounds display a preference for specific ubiquitin specific proteases (USPs).

The present invention provides a method of decreasing the level of ubiquitylated protein in a subject, the method comprising administering a heterocyclic compound disclosed herein or a pharmaceutically acceptable salt, hydrate or prodrug thereof to a subject in need thereof.

The invention discloses artificially constructed hybrid ubiquitin conjugation structure domain polypeptide and an application thereof. The hybrid ubiquitin conjugation structure domain polypeptide is formed by connecting at least tow ubiquitin conjugation structures in series, and in all ubiquitin conjugation structure domains forming the hybrid ubiquitin conjugation structure domain polypeptide, at least two ubiquitin conjugation structure domain are different. In addition, the hybrid ubiquitin conjugation structure domain polypeptide can contain tag protein. The experiment shows that the tag protein disclosed by the invention can conjugate ubiquitin molecules and different ubiquitin chains carried in the ubiquitin molecules efficiently without unbiasedness, can improve the enrichment efficiency of on-scale ubiquitin protein, is used for developing efficient ubiquitin protein separation mediums and biologic reagents, and can provide technical methods for regulating in-vivo protein ubiquitination. The polypeptide is significant for prompting human disease sample ubiquitin proteomics study and development of health medicine.

The invention provides a mutated PCV2 (Porcine circovirus Type 2) virus free from being degraded by ubiquitination proteasome, and a preparation method and application thereof. Three loci (164K, 179Kand 191K) of porcine circovirus 2 type (PCV2, GenBank and No. EU366323) strains Cap are mutated, the mutated PCV2 can not be subjected to MKRN1-mediated ubiquitination degrading, in addition, high speed copying can be carried out through infectious clone, and virus price is high than virus price of wild-type PCV2. Through mutated viruses obtained by the infectious clone, the pathogenic mechanism of the PCV2 can be more favorably researched, and a potential control measure is provided for PCV2 outbreak.

The invention relates to an application of a ubiquitination pathway related factor in regulating and controlling functions of a regulatory T cell. Specifically, the invention relates an application ofthe ubiquitination pathway related factor and an agonist or an antagonist thereof in preparing a preparation or a reagent for regulating FOXP3 or the regulatory T cell, wherein the ubiquitination related factor is selected from gene coding proteins USP44 and USP7 of a ubiquitination protein family. The novel regulatory factor provided by the invention, by regulating transcriptional regulatory activity of the FOXP3 on a target gene thereof, can regulate and control the regulatory T cell and the balance of an immune system.

The invention relates to a modified Bach1 gene and an application thereof to pluripotency, self-updating, proliferation, reprogramming and differentiation of a stem cell. Due to the modification of the Bach1 gene of a transcription factor, the BACH1 protein activity or expression of the cell is inhibited or increased, and furthermore, the cell interacts with a deubiquitinated protease Usp7, a pluripotent factor Nanog, Sox2 and/or Oct4, a PRC2 complex, a Wnt/beta-catenin signal channel and/or an Nodal/Smad2/3 signal channel, so that the self-updating, proliferation and/or differentiation of thestem cell are regulated.

The invention discloses a His-Vx3-eGFP protein-nano aluminum covalent coupling ubiquitinated protein containing carbon-nitrogen bonds as well as an extraction method and application thereof. The ubiquitinated protein is prepared through the following steps of: forming a conjugate of His-Vx3-eGFP protein and modified nano aluminum by virtue of carbon-nitrogen double bonds and incubating the conjugate and a treated tumor cell lysis solution. Compared with the prior art, obtained alpha-Al2O3-His-Vx3-eGFP is stable in property, is capable of greatly improving the ubiquitinated protein collection effect and simplifying experiment operation; in addition, the defect that adjuvants are added in use of an existing ubiquitinated protein vaccine is overcome.

The invention relates to the field of biotechnology and medical diagnosis, in particular to application of E3 ubiquitination protein ligase UBR5 in preparation of a renal clear cell carcinoma diagnosis or prognosis evaluation reagent or kit and a corresponding detection kit. Researches find that the expression of E3 ubiquitination protein ligase UBR5 molecules in patients with renal clear cell carcinoma is generally reduced, the expression level of the E3 ubiquitination protein ligase UBR5 molecules is remarkably related to prognosis of the patients, and the total lifetime (OS) and progression-free lifetime (PFS) of the patients with renal clear cell carcinoma can be better predicted by combining the expression of UBR5.

The present application describes a Fas associated Factor 1 protein and fragment thereof that bind Hsc70/Hsp70, ubiquitinated protein and valosin containing protein.

The invention discloses a fusion protein and an application thereof to construction of a system for screening a coronavirus 3CL protease inhibitor. The invention firstly provides the fusion protein. The fusion protein is formed by fusing a ubiquitination protein at an N end and a protein with a reporting function at a C end through a 3CL protease restriction enzyme cutting site amino acid fragment, wherein the 3CL protease restriction enzyme cutting site amino acid fragment is an amino acid fragment which can be recognized by 3CL protease and can be subjected to restriction enzyme cutting. A system for screening the coronavirus 3CL protease inhibitor is constructed by utilizing the fusion protein, an encoding gene of the fusion protein, a carrier containing the fusion protein or recombinant cells for expressing the fusion protein, and the system is convenient and rapid, is simple to operate and has good specificity and sensitivity; by utilizing the system, the coronavirus 3CL proteaseinhibitor can be conveniently and effectively screened, the screening mechanism is clear, the speed is high, the action effect is visual, the universality is high, the repeatability is good, the falsepositive rate is low, and the system has a good application prospect in screening of the coronavirus 3CL protease inhibitor.

Provided is a pharmaceutical composition comprising a scavenger, wherein the scavenger is used for clearing away mutant FUS. A method for treating or preventing or alleviating ALS is also provided.

The invention relates to a method for utilizing ubiquitin-binding domain (UBD) fusion protein to separate and detect ubiquitination protein. The principle is that a fusion protein is constructed by using an affinity label and a ubiquitin-binding domain. The fusion protein can be expressed in colon bacillus, purified and fixed on a gel particle through the ligand of the affinity label. Mixed culture is carried out on the gel particle with the ubiquitin-binding domain fusion protein and lysate of cell or tissue, and the ubiquitination protein in the lysate can be separated out through precipitation. On the aspect of the detection of ubiquitination protein, the method disclosed by the invention is higher in efficiency, detection capacity and flexibility compared with the current antibody immune precipitation detection method. Moreover, on the aspect of economic benefit, the cost of detecting ubiquitination protein in the invention is extremely lower than that of expensive antibody immune precipitation method; and the method can be applied to fundamental research of protein ubiquitination and the detection of ubiquitination protein in medical diagnosis test.