A5100631700- Ubiquitin and proteasome pathways
- Viral-associated cancers and disorders
- Lymphoma Diagnosis and Treatment
- Peptidase Inhibition and Analysis
- Hepatitis C virus research
- Protein Degradation and Inhibitors
- Glycosylation and Glycoproteins Research
- Animal Virus Infections Studies
- Cancer-related molecular mechanisms research
- Endoplasmic Reticulum Stress and Disease
- Sesquiterpenes and Asteraceae Studies
- Autophagy in Disease and Therapy
- Monoclonal and Polyclonal Antibodies Research
- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- CAR-T cell therapy research
- Cancer-related gene regulation
- RNA and protein synthesis mechanisms
- Protease and Inhibitor Mechanisms
- RNA regulation and disease
- Click Chemistry and Applications
- NF-κB Signaling Pathways
- Eosinophilic Disorders and Syndromes
- Cytomegalovirus and herpesvirus research
- Chemical Synthesis and Analysis
Shanghai Jiao Tong University
2016-2025
National Institutes for Quantum Science and Technology
2025
Ministry of Education of the People's Republic of China
2022-2024
Union Hospital
2024
Jilin University
2024
Peking University First Hospital
2024
Yinchuan First People's Hospital
2024
Peking University
2024
Second Military Medical University
2022-2023
University of Jinan
2023
Engineering the ubiquitin transfer cascades by phage display enables an efficient way to profile E3 substrates.
Radiotherapy for localized prostate cancer often targets the entire with a uniform dose despite presence of high-risk dominant intraprostatic lesions (DILs). This study investigated feasibility focal dose-averaged linear energy transfer (LETd) boost carbon-ion radiotherapy to deposit higher LETd DILs while ensuring desired relative biological effectiveness weighted coverage and sparing organs at risk (OARs). A retrospective planning was conducted on 15 cases. The were identified...
AGR2 is a pro-oncogenic protein overexpressed in multiple cancer types, and it promotes tumor progression. Therefore, regarded as promising therapeutic target for cancer. We reported the development antitumor mechanism of AGR2-specific monoclonal antibody 18A4. To elicit AGR2-guided synergistic response by redirecting cytotoxic T-cells, we developed first T-cell-engaging bispecific (BsAb) targeting PD1 simultaneously. This novel BsAb efficiently targets AGR2-rich solid tumors. In this study,...
Abstract Protein drugs have evolved into a primary category of biological drugs. Despite the impressive achievements, protein therapeutics still face several challenges, including potential immunogenicity, druggability, and high costs. In recent years, artificial intelligence (AI) computational biology emerged as powerful tools to overcome these challenges reshape drug development pipeline. This review underscores pivotal role AI in advancing development, analysis phage libraries,...
Severe Mycoplasma pneumoniae pneumonia (SMPP) poses significant diagnostic challenges due to its clinical features overlapping with those of other common respiratory diseases. This study aims develop and validate machine learning (ML) models for the early identification SMPP risk prediction liver heart damage in using accessible laboratory indicators. Cohort 1 was divided into group diseases group. 2 myocardial damage, non-damage groups. The built five ML algorithms were compared screen best...
Formyl peptide receptors (FPRs) are G protein-coupled chemoattractant expressed mainly in phagocytic leukocytes. High expression of FPRs has also been detected several cancers but the functions FPR1 tumor invasion and metastasis is poorly understood. In this study, we investigated primary human colorectal cancer (CRC) analyzed association with clinicopathological parameters. The levels mRNA, especially those FPR1, were significantly higher tumors than distant normal tissues adjacent...
Abstract Protein ubiquitination is mediated sequentially by ubiquitin activating enzyme E1, conjugating E2 and ligase E3. Uba1 was thought to be the only E1 until recent identification of Uba6. To differentiate biological functions Uba6, we applied an orthogonal transfer (OUT) technology profile their targets in mammalian cells. By expressing pairs engineered or Uba6 that were generated for exclusive interactions, identified 697 potential 527 with 258 overlaps. Bioinformatics analysis...
Abstract E3 ubiquitin (UB) ligases are the ending modules of E1–E2-E3 cascades that transfer UB to cellular proteins and regulate their biological functions. Identifying substrates an holds key elucidate its role in cell regulation. Here, we construct orthogonal (OUT) cascade identify E6AP, a HECT also known as Ube3a is implicated cancer neurodevelopmental disorders. We use yeast surface display engineer E6AP exclusively affinity-tagged variant (xUB) substrate proteins. Proteomic...
Abstract TNFR-associated factor (TRAF)6 integrates signals from multiple cell surface receptors for the activation of NF-κB. However, mechanism underlying LPS-induced TRAF6 signaling remains unclear. We report that cullin-5 (Cul-5), a cullin family scaffold protein, binds to and promotes polyubiquitination at Lys63 in response LPS stimulation. A direct interaction between C-terminal domain Cul-5 TRAF-C facilitates TRAF6. Hemizygous knockout is associated with improved survival mice following...
Nonalcoholic fatty liver disease (NAFLD) is substantiated by the reprogramming of metabolic pathways that disrupts homeostasis lipid and glucose metabolism thus promotes progression disease. The associated with NAFLD are regulated at different levels from gene transcription to various post-translational modifications including ubiquitination. Here, we used a novel orthogonal ubiquitin transfer platform identify pyruvate dehydrogenase A1 (PDHA1) acetyl-CoA acetyltransferase 1 (ACAT1), two...
Ubiquitin (UB) is a protein modifier that regulates many essential cellular processes. To initiate modification by UB, the E1 enzyme activates C-terminal carboxylate of UB to launch its transfer through E1-E2-E3 cascade onto target proteins. In this study, we used phage display profile specificity two human enzymes, Ube1 and Uba6, toward sequence ending with (71)LRLRGG(76). Phage selection revealed while Arg72 absolutely required for recognition, residues at positions 71, 73, 74 can be...
Glycosyltransferase OGT catalyzes the conjugation of O-linked β-D-N-acetylglucosamine (O-GlcNAc) to Ser and Thr residues cellular proteins regulates many key processes in cell. Here, we report identification as a ubiquitination target HECT-type E3 ubiquitin (UB) ligase E6AP, whose overexpression HEK293 cells would induce degradation OGT. We also found that expression E6AP HeLa with endogenous E6 protein human papillomavirus (HPV) accelerate by proteasome suppress O-GlcNAc modification...
Abstract The ubiquitin‐like protein SUMO is transferred through a core E1–E2 cascade composed of the SUMO‐activating enzyme (SAE) and Ubc9 to modify cellular proteins transmit important biological signals. SAE primarily recognizes C‐terminal tail catalyzes ATP condensation with carboxylate activate its transfer cascade. Here, we used phage display show that broad profile sequences could be activated by SAE. Based on this, developed heptamer peptides 1) form thioester conjugates SAE, 2) from...