Anti-K63-linked polyubiquitin monoclonal antibodies, and methods for using the antibodies, are provided.

The present subject matter relates to the use of one or more inhibitors to treat a disease, e.g., cancer, in a subject. It is based, at least in part, on the discovery that protein kinase B (AKT) and ring finger protein 167 (RNF167)-mediated CASTOR1 degradation activates the mammalian target of rapamycin complex 1 (mTORC1) independent of arginine and promotes cancer progression. Accordingly, the presently disclosed subject matter provides for compositions, methods, and kits for treating a subject using an RNF167 inhibitor, an inhibitor that reduces phosphorylation of CASTOR1 at S14, ubiquitination and/or degradation of CASTOR1, or a combination thereof.

Methods for the large scale identification of post-translational modification states of proteins and enzyme activities for carrying out post-translational modification reactions involve the analysis of functional extracts from fresh and frozen samples using protein arrays. The methods and kits of the present invention can be used to analyze and characterize compounds for their effects on post-translational modifications and their pathways. The methods and kits can also be used to diagnose and characterize a wide variety of diseases and medical conditions, including cancer, neurodegenerative diseases, immune diseases, infectious diseases, genetic diseases, metabolic conditions, and drug effects using cells or body fluids of a patient.

The invention provides antibodies that bind mixed-topology polyubiquitin and multispecific anti-polyubiquitin antibodies, and methods of using the same.

The invention provides antibodies that bind mixed-topology polyubiquitin and multispecific anti-polyubiquitin antibodies, and methods of using the same.

The present invention relates to peptides and peptidomimetics as well as their medical use in the treatment of hyperproliferative diseases and inflammatory diseases.

The invention provides a method of diagnosing arthritis or other joint degrading disease in a subject which comprises determining whether there is a presence or increase of lubricin having a joint tissue posttranslational modification, in a blood sample from the subject, the presence or increase of the lubricin having the joint tissue posttranslational modification indicating arthritis or other joint degrading disease in the subject. The invention further provides a kit or protocol for detecting arthritis or other joint degrading disease by detecting lubricin, the lubricin comprising a joint tissue posttranslational modification.

The present invention relates to a method for identifying compounds or agents able to induce ubiquitination of a protein of interest. Further, the present invention relates to compounds/agents obtainable by the method of the present invention. Furthermore, the present invention relates to a method for treating cancer or other diseases comprising administering the chemical compound or agent obtainable by the method of the present invention. Moreover, the present invention relates to a eukaryotic cell comprising enhanced cullin-RING ubiquitin ligase (CRL) activity and/or constantly neddylated cullin-RING ubiquitin ligases/CRLs.

Disclosed are methods for identifying an agent of interest that alters binding or activity of a client protein to a chaperone and kits thereof.

Anti-K63-linked polyubiquitin monoclonal antibodies, and methods for using the antibodies, are provided.