The present disclosure describes pan-SUMO trapping proteins and fusion proteins comprising the pan-SUMO trapping proteins that are stable and bind SUMO-modified proteins with high avidity. The proteins described herein can be used to detect the localization of SUMO-modified proteins cells. The proteins described herein can be used to identify biomarkers for diseases associated with oxidative stress. They can also be used to diagnose and monitor diseases associated with genotoxic and/or proteotoxic stress conditions.

A radical departure from the classical E1-E2-E3 three-enzyme mediated ubiquitination of eukaryotes, the bacterial enzymes of the SidE family of Legionella pneumophila effectors utilize NAD.sup.+ to ligate ubiquitin onto target substrate proteins achieved via a two-step mechanism involving (1) ADP-ribosylation of ubiquitin followed by (2) phosphotransfer to a target serine residue. Using fluorescent NAD.sup.+ analogues as well as synthetic substrate mimics, a continuous assay system enabling real-time monitoring of both steps of this mechanism is disclosed herein. These assays are amenable to biochemical studies and high-throughput screening of inhibitors of these effectors, and enable the discovery and characterization of putative enzymes similar to the SidE family in other organisms. A kit of the assay system, for real-time monitoring protein ubiquitination and/or identifying an inhibitor for protein ubiquitination comprising a fluorescent NAD+ analogue and a synthetic substrate mimic, is also in the scope of this disclosure.

This document provides methods and materials involved in identifying mammals (e.g., humans) having cancer cells with an elevated level of phosphorylated Ub polypeptides (e.g., an elevated level of Y59 phosphorylated Ub polypeptides). For example, methods and materials for detecting the presence of cancer cells having an elevated level of Y59 phosphorylated Ub polypeptides are provided.

The present invention relates to compounds and compositions capable of acting as inhibitors of small ubiquitin-like modifier (SUMO) family of proteins. The compounds and compositions may be used in the treatment of cancer. There are disclosed, inter alia, methods of inhibiting an E1 enzyme, and compounds useful for inhibiting an E1 enzyme.

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 present disclosure provides compositions and methods for treating acute myeloid leukemia (AML) using a histone deacetylase (HDAC) inhibitor alone or incombination with a RING finger protein 5 (RNF5) inhibitor and/or a retinoblastoma binding protein 4 (RBBP4) inhibitor. Moreover, RNF5 and/or RBBP4 expression or protein levels in a patient can be measured and used to inform individualized treatment options and dosing regiments. For example, AML patients with lower levels of either RNF5 or RBBP4 may be stratified and treated with one or more HDAC inhibitors leading to improved therapeutic results.

This document provides methods and materials involved in identifying mammals (e.g., humans) having cancer cells with an elevated level of phosphorylated Ub polypeptides (e.g., an elevated level of Y59 phosphorylated Ub polypeptides). For example, methods and materials for detecting the presence of cancer cells having an elevated level of Y59 phosphorylated Ub polypeptides are provided.

This present technology relates to the use of inflammation-enabling polypeptides (or their coding sequences) to screen for agents useful for the prevention, treatment and/or alleviations of symptoms associated with an inflammatory disorder, to identify individuals susceptible of developing an exacerbated inflammatory response as well as to determine if a therapeutic regimen is capable of preventing, treating or alleviating the symptoms associated to an inflammatory disorder in an individual. The present technology also provides methods for preventing, treating and/or alleviating the symptoms associated to an inflammatory condition based on the inhibition of expression or activity of the inflammation-enabling targets.

Bacterial systems for screening for small molecule agents are disclosed herein. Kits for carrying out the screening are also disclosed.

The invention provides anti-polyubiquitin antibodies and methods of using the same.