A5000671597- Ubiquitin and proteasome pathways
- Protein Degradation and Inhibitors
- Galectins and Cancer Biology
- Epigenetics and DNA Methylation
- Glycosylation and Glycoproteins Research
- Peptidase Inhibition and Analysis
- Cancer-related gene regulation
- Histone Deacetylase Inhibitors Research
- Endoplasmic Reticulum Stress and Disease
- Autophagy in Disease and Therapy
- Protein Tyrosine Phosphatases
- interferon and immune responses
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Cancer, Hypoxia, and Metabolism
- Cancer-related Molecular Pathways
- Multiple Myeloma Research and Treatments
- Cell death mechanisms and regulation
- Virus-based gene therapy research
- Mitochondrial Function and Pathology
- Phytoplasmas and Hemiptera pathogens
- CRISPR and Genetic Engineering
- Caveolin-1 and cellular processes
- Mesenchymal stem cell research
- Prostate Cancer Treatment and Research
Tianjin Medical University
2021-2025
Tianjin Medical University General Hospital
2022-2024
Ocean University of China
2008-2023
Van Andel Institute
2018-2019
The University of Texas MD Anderson Cancer Center
2016-2018
Geisinger Medical Center
2014
Geisinger Health System
2014
GlcNAcylation, a dynamic posttranslational modification, is involved in wide range of biological processes and some human diseases. Although there emerging evidence that tumor-associated proteins are modified by the role GlcNAcylation tumor progression remains unclear. Here, we show enhances migration/invasion breast cancer cells vitro lung metastasis vivo. The decrease cell surface E-cadherin molecular mechanism underlying GlcNAcylation-induced metastasis. p120 beta-catenin, but not...
Recognition of modified histones by "reader" proteins constitutes a key mechanism regulating diverse chromatin-associated processes important for normal and neoplastic development. We recently identified the YEATS domain as novel acetyllysine-binding module; however, functional importance domain-containing in human cancer remains largely unknown. Here, we show that YEATS2 gene is highly amplified non-small cell lung (NSCLC) required growth survival. binds to acetylated histone H3 via its...
Abstract SIRT1 is the most evolutionarily conserved mammalian sirtuin, and it plays a vital role in regulation of metabolism, stress responses, genome stability, ageing. As sensor, deacetylase activity significantly increased during stresses, but molecular mechanisms are not yet fully clear. Here, we show that dynamically modified with O-GlcNAc at Ser 549 its carboxy-terminal region, which directly increases both vitro vivo. The O-GlcNAcylation elevated genotoxic, oxidative, metabolic...
Abstract Acetylation of histone H3K23 has emerged as an essential posttranslational modification associated with cancer and learning memory impairment, yet our understanding this epigenetic mark remains insufficient. Here, we identify the native MORF complex a H3K23-specific acetyltransferase elucidate its mechanism action. The function catalytic subunit is positively regulated by DPF domain (MORF ). crystal structure in crotonylated H3K14 peptide provides mechanistic insight into...
Abstract Autophagic receptor p62 is a critical mediator of cell detoxification, stress response, and metabolic programs commonly deregulated in human diseases. The diverse functions arise from its ability to interact with large set ligands, such as arginylated (Nt-R) substrates. Here, we describe the structural mechanism for selective recognition Nt-R by ZZ domain (p62 ). We show that binding substrates stimulates aggregation macroautophagy required autophagic targeting p62. essential mTORC1...
BMI1, a polycomb group (PcG) protein, plays critical role in epigenetic regulation of cell differentiation and proliferation, cancer stem self-renewal. BMI1 is upregulated multiple types cancer, including prostate cancer. As key component repressive complex 1 (PRC1), exerts its oncogenic functions by enhancing the enzymatic activities RING1B to ubiquitinate histone H2A at lysine 119 repress gene transcription. Here, we report PRC1-independent that for castration-resistant (CRPC) progression....
Abstract Recognition of histones by epigenetic readers is a fundamental mechanism for the regulation chromatin and transcription. Most reader modules target specific post-translational modifications on histones. Here, we report identification histone H3, ZZ-type zinc finger (ZZ) domain ZZZ3, subunit Ada-two-A-containing (ATAC) acetyltransferase complex. The solution NMR structure ZZ in complex with H3 peptide reveals unique binding involving caging N-terminal Alanine 1 an acidic cavity...
Abstract SAP05, a secreted effector by the obligate parasitic bacteria phytoplasma, bridges host SPL and GATA transcription factors (TFs) to 26 S proteasome subunit RPN10 for ubiquitination-independent degradation. Here, we report crystal structures of SAP05 in complex with SPL5, GATA18 RPN10, which provide detailed insights into protein-protein interactions involving SAP05. employs two opposing lobes an acidic path hydrophobic contact TFs respectively. Our structures, conjunction...
Abstract Background Lipocalin 2, an iron binding protein, is abnormally expressed in some malignant human cancers and may play important role tumor metastasis. However, the roles of lipocalin 2 breast cancer formation metastasis have not been clearly shown. This study aimed to investigate Methods was overexpressed metastatic 4T1 murine mammary cells. The effects overexpression on malignancy cells were examined using cell proliferation assay, migration invasion soft agar assay vitro . Tumor...
Abstract Background Gangliosides are sialic acid containing glycosphingolipids that ubiquitously distributed on vertebrate plasma membranes. GM3, a precursor for most of the more complex ganglioside species, is synthesized by GM3 synthase. Although total levels significantly higher in breast tumor tissue than normal mammary tissue, roles played gangliosides cancer formation and metastasis not clear. Methods To investigate development, synthase was silenced highly metastatic 4T1 cells...
Abstract The YEATS domain has been identified as a reader of histone acylation and more recently emerged promising anti-cancer therapeutic target. Here, we detail the structural mechanisms for π-π-π stacking involving domains yeast Taf14 human AF9 acylated H3 peptides explore DNA-binding activities these domains. Taf14-YEATS selects crotonyllysine, forming π with both crotonyl amide alkene moiety, whereas AF9-YEATS exhibits comparable affinities to saturated unsaturated acyllysines, engaging...
As a crucial element of proteolysis targeting chimeras (PROTACs), the choice E3 ubiquitin ligase significantly influences degradation efficacy and selectivity. However, available arsenal ligases for PROTAC development remains underexplored, severely limiting scope targeted protein degradation. In this study, we identify non-inhibitory aptamer ZYG11B, substrate receptor Cullin 2-RING complex, as an warhead This aptamer-based platform, termed ZATAC, is facilely produced through bioorthogonal...
Newborns exhibit a heightened vulnerability to inflammatory disorders due their underdeveloped immune system, yet the underlying mechanisms remain poorly understood. Here we report that plasma spermidine is correlated with maturity of human newborns and reduced risk inflammation. Administration led remission neonatal inflammation in mice. Mechanistic studies revealed enhanced generation polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) via downstream eIF5A hypusination. Genetic...
The exposed N-terminal or C-terminal residues of proteins can act, in cognate sequence contexts, as degradation signals (degrons) that are targeted by specific E3 ubiquitin ligases for proteasome-dependent
Proteolysis-targeting chimeras (PROTACs) provide a powerful technique to degrade targeted proteins utilizing the cellular ubiquitin-proteasome system. The major concern is host toxicity resulting from their poor selectivity. Inducible PROTACs responding exogenous stimulus, such as light, improve specificity, but it difficult for photo-activation in deep tissues. Herein, we develop H2 O2 -inducible PROTAC precursors 2/5, which can be activated by endogenous cancer cells release active 1/4...
Abstract Ageing and cell senescence of mesenchymal stem cells (MSCs) limited their immunomodulation properties therapeutic application. We previously reported that nucleosome assembly protein 1‐like 2 (Nap1l2) contributes to MSCs osteogenic differentiation. Here, we sought evaluate whether Nap1l2 impairs the immunomodulatory find a way rescue deficient properties. demonstrated metformin could impaired migration T regulation OE‐Nap1l2 BMSCs. Moreover, improve efficacy BMSCs in treatment...