A5013188041- Ubiquitin and proteasome pathways
- Cancer-related Molecular Pathways
- DNA Repair Mechanisms
- Autophagy in Disease and Therapy
- Endoplasmic Reticulum Stress and Disease
- Microtubule and mitosis dynamics
- Histone Deacetylase Inhibitors Research
- Genomics and Chromatin Dynamics
- Peptidase Inhibition and Analysis
- Genetics and Neurodevelopmental Disorders
- NF-κB Signaling Pathways
- Cancer-related gene regulation
- Cell death mechanisms and regulation
- TGF-β signaling in diseases
- Protein Degradation and Inhibitors
- Glycosylation and Glycoproteins Research
- interferon and immune responses
- Epigenetics and DNA Methylation
- Cytokine Signaling Pathways and Interactions
- Psoriasis: Treatment and Pathogenesis
- Signaling Pathways in Disease
- Virus-based gene therapy research
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Hippo pathway signaling and YAP/TAZ
Shaoxing University
2022-2025
Zhejiang University
2018-2025
Center for Life Sciences
2022-2025
Wenzhou Medical University
2025
Zhejiang Cancer Hospital
2022-2024
First Affiliated Hospital Zhejiang University
2020-2022
State Key Laboratory of Silicon Materials
2022
Life Science Institute
2021
The University of Texas Health Science Center at Houston
2010-2020
The University of Texas at Austin
2013-2016
The Nrf2 transcription factor promotes survival following cellular insults that trigger oxidative damage.Nrf2 activity is opposed by the BTB/POZ domain protein Keap1.Keap1 proposed to regulate strictly through its capacity inhibit nuclear import.Recent work suggests inhibition of may also depend upon ubiquitin-mediated proteolysis.To address contribution Keap1-dependent sequestration versus proteolysis, we identified E3 ligase regulates ubiquitination.We demonstrate Keap1 not solely a...
Myc proteins regulate cell growth and division are implicated in a wide range of human cancers. We show here that Fbw7, component the SCF Fbw7 ubiquitin ligase tumor suppressor, promotes proteasome-dependent c-Myc turnover vivo ubiquitination vitro . Phosphorylation on threonine-58 (T58) by glycogen synthase kinase 3 regulates binding to as well Fbw7-mediated degradation ubiquitination. T58 is most frequent site c- myc mutations lymphoma cells, our findings suggest activation one key...
Abstract Background microRNAs (miRNAs) are small, noncoding RNA molecules that now thought to regulate the expression of many mRNAs. They have been implicated in etiology a variety complex diseases, including Tourette's syndrome, Fragile × and several types cancer. Results We hypothesized schizophrenia might be associated with altered miRNA profiles. To investigate this possibility we compared 264 human miRNAs from postmortem prefrontal cortex tissue individuals ( n = 13) or schizoaffective...
Eukaryotic cells respond to DNA damage and stalled replication forks by activating protein kinase-mediated signaling pathways that promote cell cycle arrest repair. A central target of the program is Cdc25A phosphatase. required for S-phase entry dephosphorylates tyrosine-15 phosphorylated Cdk1 (Cdc2) Cdk2, positive regulators division. unstable during degraded through ubiquitin-proteasome pathway, but its turnover enhanced in response damage. Although basal DNA-damage-induced depends on...
ABSTRACT Human papillomavirus type 16 (HPV16) and other high-risk HPVs are etiologically linked to the development of cervical carcinomas contribute a number tumors anogenital tract, as well oral cancers. The HPV E6 E7 oncoproteins consistently expressed in cancer cells necessary for induction maintenance transformed phenotype. An important aspect HPV16 E7's oncogenic activities is destabilization retinoblastoma tumor suppressor (pRB) through ubiquitin/proteasome-dependent mechanism,...
IFN-beta-1a has been used over the past 15 years as a primary therapy for relapsing-remitting multiple sclerosis (MS). However, immunomodulatory mechanisms that provide therapeutic effect against this CNS inflammatory disease are not yet completely elucidated. The of on Th17 cells, which play critical role in development autoimmune response, extensively studied humans. We have investigated dendritic cells (DCs) and naive CD4(+)CD45RA(+) T derived from untreated MS patients healthy controls...
Statins, extensively used as cholesterol-lowering agents, have recently been identified immunomodulatory agents. This study investigated the statins' mechanisms that target autoimmune response in humans, and evaluated their therapeutic potential multiple sclerosis. Our results demonstrated statin-mediated increases suppressor of cytokine secretion (SOCS) 3 7, which negatively regulate STAT/JAK signal transduction pathway IL-6 IL-23 gene expression monocytes. Simvastatin also induced...
Sphingosine-1-phosphate (S1P) is a bioactive lipid that regulates multicellular functions through interactions with its receptors on cell surfaces. S1P enriched and stored in erythrocytes; however, it not clear whether alterations are involved the prevalent debilitating hemolytic disorder sickle disease (SCD). Here, using metabolomic screening, we found highly elevated blood of mice humans SCD. In murine models SCD, demonstrated erythrocyte sphingosine kinase 1 (SPHK1) underlies sickling...
Significance Legionella pneumophila , the Legionnaires’ disease-causing bacterial pathogen, translocates a myriad of proteins, called effectors, into host cells. These proteins exploit normal cellular functions to facilitate intracellular growth. To identify these effectors has been major challenge. Here, we determined structure one such effector, substrate Icm/Dot transporter (SidC), which was previously thought be vesicle-tethering factor for recruiting endoplasmic reticulum (ER) vesicles...
Transcription factors (TFs) are families of proteins that bind to specific DNA sequences, or TF response elements (TFREs), and function as regulators many cellular processes. Because the low abundance TFs, direct quantitative measurement TFs on a proteome scale remains challenge. In this study, we report development an affinity reagent permits identification endogenous at scale. The is composed synthetic containing concatenated tandem array consensus TFREs (catTFRE) for majority families. By...
Roles of liver-specific genes (LSGs) in tumor initiation and progression are rarely explored hepatocellular carcinoma (HCC). Here we show that LSGs generally downregulated HCC tissues compared to non-HCC liver tissues, low-LSG HCCs poor prognosis the activated c-Myc pathway. Among c-Myc- patient prognosis-associated LSGs, PGRMC1 significantly blocks c-Myc-induced orthotopic formation. The role depends on its localization endoplasmic reticulum (ER) membrane, where interacts with PERK through...
The mitochondrial proapoptotic protein Smac/DIABLO has recently been shown to potentiate apoptosis by counteracting the antiapoptotic function of inhibitor proteins (IAPs). In response apoptotic stimuli, Smac is released into cytosol and promotes caspase activation binding IAPs, thereby blocking their function. These observations have suggested that a new regulator apoptosis. To better understand physiological in normal cells, we generated Smac-deficient (Smac(-/-)) mice using homologous...
IFN-beta, an effective therapy against relapsing-remitting multiple sclerosis, is naturally secreted during the innate immune response viral pathogens. The objective of this study was to characterize immunomodulatory mechanisms IFN-beta targeting and their effects on dendritic cell (DC)-mediated regulation T differentiation. We found that IFN-beta1a in vitro treatment human monocyte-derived DCs induced expression TLR7 members its downstream signaling pathway, including MyD88,...
Abstract Faster acclimatization to high altitude upon re-ascent is seen in humans; however, the molecular basis for this enhanced adaptive response unknown. We report that healthy lowlanders, plasma adenosine levels are rapidly induced by initial ascent and achieved even higher re-ascent, a feature positively associated with quicker acclimatization. Erythrocyte equilibrative nucleoside transporter 1 (eENT1) reduced humans at mice under hypoxia. eENT1 deletion allows rapid accumulation of...
Disease progression of primary pneumonic plague is biphasic, consisting a preinflammatory and proinflammatory phase. During the long phase, bacteria replicate to high levels, seemingly uninhibited by normal pulmonary defenses. In coinfection model plague, it appears that Yersinia pestis quickly creates localized, dominant anti-inflammatory state allows for survival rapid growth both itself normally avirulent organisms. pseudotuberculosis , relatively recent progenitor Y. shows no similar...