HENA, heterogeneous network-based data set for Alzheimer's disease.

Alzheimer's disease and other types of dementia are the top cause for disabilities in later life and various types of experiments have been performed to understand the underlying mechanisms of the disease with the aim of coming up with potential drug targets. These experiments have been carried out by scientists working in different domains such as proteomics, molecular biology, clinical diagnostics and genomics. The results of such experiments are stored in the databases designed for collecting data of similar types.

Discovery of specific inhibitors of human USP7/HAUSP deubiquitinating enzyme.

The human USP7 deubiquitinating enzyme was shown to regulate many proteins involved in the cell cycle, as well as tumor suppressors and oncogenes. Thus, USP7 offers a promising, strategic target for cancer therapy. Using biochemical assays and activity-based protein profiling in living systems, we identified small-molecule antagonists of USP7 and demonstrated USP7 inhibitor occupancy and selectivity in cancer cell lines.

Ubiquitin-specific proteases as cancer drug targets.

Ubiquitin-specific proteases are deubiquitinating enzymes involved in the removal of ubiquitin from specific protein substrates resulting in protein salvage from proteasome degradation, regulation of protein localization or activation. DNA alteration and overexpression in different cancer types, as well as involvement in many cancer-associated pathways, make ubiquitin-specific proteases attractive for the cancer drug discovery purposes. Their proteolytic function associated to available structural biology data reinforce their potential for pharmacological interference.

Small-molecule inhibitor of USP7/HAUSP ubiquitin protease stabilizes and activates p53 in cells.

Deregulation of the ubiquitin/proteasome system has been implicated in the pathogenesis of many human diseases, including cancer. Ubiquitin-specific proteases (USP) are cysteine proteases involved in the deubiquitination of protein substrates. Functional connections between USP7 and essential viral proteins and oncogenic pathways, such as the p53/Mdm2 and phosphatidylinositol 3-kinase/protein kinase B networks, strongly suggest that the targeting of USP7 with small-molecule inhibitors may be useful for the treatment of cancers and viral diseases.

From protein-protein complexes to interactomics.

Protein-protein interactions (or PPIs) are key elements for the normal functioning of a living cell. A large description of the protein interactomics field is given in this review where different aspects will be discussed. We first give an introduction of the different large scale experimental approaches from yeast two-hybrid to mass spectrometry used to discover PPIs and build protein interaction maps.

Protein interaction mapping: a Drosophila case study.

The Drosophila (fruit fly) model system has been instrumental in our current understanding of human biology, development, and diseases. Here, we used a high-throughput yeast two-hybrid (Y2H)-based technology to screen 102 bait proteins from Drosophila melanogaster, most of them orthologous to human cancer-related and/or signaling proteins, against high-complexity fly cDNA libraries. More than 2300 protein-protein interactions (PPI) were identified, of which 710 are of high confidence.