Publications

HuProt PPI: DNA damage-activated nuclease identified - Cells that experience stresses and accumulate excessive damage to DNA undergo cell death mediated by a nuclear enzyme known as PARP-1. During this process, apoptosis-inducing factor (AIF) translocates to the nucleus and activates one or more nucleases to cleave DNA. Wang et al. found that macrophage migration inhibitory factor (MIF) is an AIF-associated endonuclease that contributes to PARP-1-induced DNA fragmentation (see the Perspective by Jonas).

• Link: https://www.science.org/doi/10.1126/science.aad6872

Antibodies cross-reactive to pathogens and autoantigens are considered pivotal in both infection control and accompanying autoimmunity. However, the pathogenic roles of autoantibodies largely remain elusive without a priori knowledge of disease-specific autoantigens. Here, through a novel quantitative proteogenomics approach, we demonstrated a successful identification of immunoglobulin variable heavy chain (VH) sequences highly enriched in pathological immune complex from clinical specimens obtained from a patient with hepatitis C virus-induced cryoglobulinemia (HCV-CG).

• Link: https://www.nature.com/articles/srep29532

Autoantibodies are used clinically to phenotype and subset patients with autoimmune rheumatic diseases. We detected a novel 60 kDa autoantibody specificity by immunoblotting using a dermatomyositis (DM) patient\'s serum. Our objective was to identify the targeted autoantigen and to evaluate disease specificity and clinical significance of this new autoantibody.

• Link: https://ard.bmj.com/content/75/6/1145

The use of protein microarrays to evaluate antibodies is likely to set new quality standards to evaluate antibody cross-reactivity, and will also address the need for new methods to identify antibodies that can be used in robust scientific investigations, grant proposals and for commercialization.

• Link: https://filgen.jp/Product/Bioscience4/CDI/CDI_HighSpec_WhitePaper_Full.pdf

We aimed to globally discover serum biomarkers for diagnosis of gastric cancer (GC). GC serum autoantibodies were discovered and validated using serum samples from independent patient cohorts encompassing 1,401 participants divided into three groups, i.e. healthy, GC patients, and GC-related disease group. To discover biomarkers for GC, the human proteome microarray was first applied to screen specific autoantibodies in a total of 87 serum samples from GC patients and healthy controls.

• Link: https://www.mcponline.org/article/S1535-9476(20)33691-4/fulltext#%20

HuProt PPI: The secretion of IL-1β is a central event in the initiation of inflammation. Unlike most other cytokines, the secretion of IL-1β requires two signals: one signal to induce the intracellular up-regulation of pro-IL-1β and a second signal to drive secretion of the bioactive molecule. The release of pro-IL-1β is a complex process involving proteolytic cleavage by caspase-1. However, the exact mechanism of secretion is poorly understood. Here we sought to identify novel proteins involved in IL-1β secretion and intracellular processing to gain further insights into the mechanism of IL-1 release. A human proteome microarray containing 19,951 unique proteins was used to identify proteins that bind human recombinant pro-IL-1β.

• Link: https://www.jbc.org/article/S0021-9258(20)39311-X/fulltext#%20

HuProt Small Molecule: Arsenic is highly effective for treating acute promyelocytic leukemia (APL) and has shown significant promise against many other tumors. However, although its mechanistic effects in APL are established, its broader anticancer mode of action is not understood. In this study, using a human proteome microarray, we identified 360 proteins that specifically bind arsenic. Among the most highly enriched proteins in this set are those in the glycolysis pathway, including the rate-limiting enzyme in glycolysis, hexokinase-1. Detailed biochemical and metabolomics analyses of the highly homologous hexokinase-2 (HK2), which is overexpressed in many cancers, revealed significant inhibition by arsenic.

• Link: https://www.pnas.org/doi/full/10.1073/pnas.1521316112

P21-activated kinase 4 (PAK4) is a Cdc42 effector protein thought to regulate cell adhesion disassembly in a kinase-dependent manner. We found that PAK4 expression is significantly higher in high-grade human breast cancer patient samples, whereas depletion of PAK4 modifies cell adhesion dynamics of breast cancer cells. Surprisingly, systematic analysis of PAK4 functionality revealed that PAK4-driven adhesion turnover is neither dependent on Cdc42 binding nor kinase activity.

• Link: https://rupress.org/jcb/article/211/4/863/38638/PAK4-promotes-kinase-independent-stabilization-of

HuProt Enzyme: Scaffold proteins play a crucial role in facilitating signal transduction in eukaryotes by bringing together multiple signaling components. In this study, we performed a systematic analysis of scaffold proteins in signal transduction by integrating protein-protein interaction and kinase-substrate relationship networks. We predicted 212 scaffold proteins that are involved in 605 distinct signaling pathways. The computational prediction was validated using a protein microarray-based approach.

• Link: https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1004508

The heterogeneity and poor prognosis associated with gliomas, makes biomarker identification imperative. Here, we report autoantibody signatures across various grades of glioma serum samples and sub-categories of glioblastoma multiforme using Human Proteome chips containing ~17000 full-length human proteins. The deduced sets of classifier proteins helped to distinguish Grade II, III and IV samples from the healthy subjects with 88, 89 and 94% sensitivity and 87, 100 and 73% specificity, respectively.

• Link: https://www.nature.com/articles/srep13895