74 results about "Proteasome degradation" patented technology

Disclosed herein are vaccines and methods for inducing an immune response against cancer cells and cells infected with intracellular parasites. Vaccines having housekeeping epitopes are disclosed. The housekeeping epitope is formed by housekeeping proteasomes in peripheral cells, but not by professional antigen presenting cells. A vaccine containing a housekeeping epitope that is derived from an antigen associated with a peripheral target cell can thus direct an immune response against the target cell. Methods of treatment are also disclosed, which involve administering a vaccine having a housekeeping epitope.

Provided are previously uncharacterised markers of cancers, for example colorectal cancers, and uses of these as diagnostic and prognostic markers of cancers, and in particular colorectal cancers. The markers are SEQ ID NO: 1—hnRNP-K; SEQ ID NO:2—HMG-1; SEQ ID NO:3—proteasome subunit alpha type 1; SEQ ID NO:4—bifunctional purine biosynthesis protein; SEQ ID NO:5—ST11; SEQ ID NO:6—annex in IV; SEQ ID NO:7—60 kDa heat shock protein; SEQ ID NO:8—T complex protein 1 beta subunit; SEQ ID NO:9—T complex protein 1 epsilon subunit; SEQ ID NO: 10—mortalin; and SEQ ID NO: 11—TER-ATPase. The invention further provides related methods and materials for the use of the markers in therapeutic intervention in colorectal and other cancers e.g. to specifically target neoplastic cells without causing significant toxicity in healthy tissues, and to provide methods for the evaluation of the ability of candidate therapeutic compounds to modulate the biological activity of cancerous cells from the colon, rectum and other tissues.

Vif binds to APOBEC3G and induces its rapid degradation, thus eliminating it from cells and preventing its incorporation into HIV-1 virions. Vif contains two domains, one that binds APOBEC3G and another with a conserved SLQ(Y / F)LA motif that mediates APOBEC3G degradation by a proteasome-dependent pathway. Provided herein are methods of exploiting these discoveries to develop compounds useful to inhibit Vif degradation of APOBEC3G, and thereby inhibit viral infection and / or replication.

Disclosed herein are vaccines and methods for inducing an immune response against cancer cells and cells infected with intracellular parasites. Vaccines having housekeeping epitopes are disclosed. The housekeeping epitope is formed by housekeeping proteasomes in peripheral cells, but not by professional antigen presenting cells. A vaccine containing a housekeeping epitope that is derived from an antigen associated with a peripheral target cell can thus direct an immune response against the target cell. Methods of treatment are also disclosed, which involve administering a vaccine having a housekeeping epitope.

The present invention relates to a compositions for and methods for cancer treatment, for example, hematopoietic cancers (e.g. B-cell Lymphoma). In other aspects, the invention provides methods for treating particular types of hematopoietic cancers, such as B-cell lymphoma, using a combination of one or more of the disclosed compounds and, for example, 26S proteasome inhibitors, such as, for example, Bortezomib. In another aspect the present invention relates to autoimmune treatment with the disclosed compounds. In another aspect, this invention relates to methods for identifying compounds, for example, compounds of the BH3 mimic class, that have unique in vitro properties that predict in vivo efficacy against B-cell lymphoma tumors and other cancers as well as autoimmune disease.

Methods, compositions and devices for inhibiting restenosis are provided. Specifically, proteasome inhibitor compositions and medical devices useful for the site specific delivery of proteasome inhibitors are disclosed. In one embodiment the medical device is a vascular stent coated with a proteasome inhibitor selected from the group consisting of a boronic acid, a C-terminal peptide aldehyde and derivatives and analogues thereof. In another embodiment an injection catheter for delivery an anti-restenotic effective amount of proteasome inhibitor to the adventitia is provided.

In accordance with the present invention, there are provided novel Siah-Mediated-Degradation-Proteins (SMDPs) and / or SCF-Complex Proteins (SCPs). Nucleic acid sequences encoding such proteins and assays employing same are also disclosed. The invention SMDPs and / or SCPs can be employed in a variety of ways, for example, for the production of anti-SMDP and / or SCP antibodies thereto, in therapeutic compositions, and methods employing such proteins and / or antibodies for drug screening, functional genomics and other applications. Also provided are transgenic non-human mammals that express the invention protein. Also provided are compositions and methods for targeting the destruction of selected polypeptides in eukaryotic cells based on the ubiquitin-independent mechanism by which ornithine decarboxylase is degraded by the 26S proteasome.

The invention discloses an application of PA200 proteins in preparation of products. The products have at least one of the following functions from (1) to (4): (1) combining with acetylated proteins; (2) promoting the degradation of the acetylated proteins; (3) participating in repair of DNA (deoxyribonucleic acid) damages of somatic cells; and (4) participating in the formation of sperms. The invention has breakthroughs in four following aspects: (1) finding a mechanism of regulation and control of degradation of the histones, the sperm formation and the DNA repair by acetylation; (2) revealing the degradation of the histones medicated by acetylation rather than ubiquitination through PA200 / Blm10 proteasome; (3) finding novel testis-specific proteasome containing PA200 and alpha 4s, and revealing the core histones as a first type biological substrate for the proteasome; and (4) revealing that a histone deacetylase inhibitor can promote the degradation of the histones which are induced by DNA double-strand breaks and medicated by acetylation, enhance the sensitivity of cells to DNA damages and easily lead to the death of the cells.

Disclosed is a total synthesis of a biologically active β-Lactam—Compound 3, which is related to Salinosporamide A and Omuralide, both structurally and by its activity as a proteasome inhibitor.Also disclosed are proteasome inhibiting compounds having the formula:wherein:R1 is a cyclolower alkyl group; or R1 is a lower alkyl group; and R2 is either hydrogen or a lower alkyl group; R3 is either hydrogen or a lower alkyl group; R4 a halo-lower alkyl group; and R5 is either hydrogen or a lower alkyl group.

The invention relates to the field of proteins, more specifically to those proteins that are located on the surface of the cell. The invention, among other things, provides an inhibitor or pharmaceutical composition capable of inhibiting down-regulation of a cell surface receptor. The invention provides a method to control or up-regulate hormone activity by using inhibitors or reagents that modify down-regulation of a protein. The invention further provides a method to control or up-regulate protein activity wherein ligand-induced receptor uptake and / or degradation by endocytosis of a receptor is inhibited, preferably by inhibiting the ubiquitin / proteasome system.