A5045972718- NF-κB Signaling Pathways
- Immune Response and Inflammation
- interferon and immune responses
- RNA modifications and cancer
- Cytokine Signaling Pathways and Interactions
- Cell death mechanisms and regulation
- Lymphoma Diagnosis and Treatment
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Cancer-related molecular mechanisms research
- MicroRNA in disease regulation
- Cell Adhesion Molecules Research
- Ubiquitin and proteasome pathways
- Viral-associated cancers and disorders
- RNA regulation and disease
- T-cell and Retrovirus Studies
- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- Pancreatic function and diabetes
- Natural product bioactivities and synthesis
- Protein Degradation and Inhibitors
- SARS-CoV-2 and COVID-19 Research
- Carbohydrate Chemistry and Synthesis
- Biochemical Analysis and Sensing Techniques
- Cancer-related Molecular Pathways
University of Macau
2016-2025
Institute of Microbiology
2022
Chinese Academy of Sciences
2022
Columbia University
2016-2019
University of California, San Diego
2006-2017
The transcription cycle of RNA polymerase II (Pol II) is regulated at discrete transition points by cyclin-dependent kinases (CDKs). Positive elongation factor b (P-TEFb), a complex Cdk9 and cyclin T1, promotes release paused Pol into elongation, but the precise mechanisms targets action remain largely unknown. Here, chemical genetic strategy, we identified ∼100 putative substrates human P-TEFb, which were enriched for proteins implicated in catabolism. Among processing factors...
Nicotinamide, the amide form of vitamin B3, is widely used in disease treatments and stem cell applications. However, nicotinamide's impact often cannot be attributed to its nutritional functions. In a screen, we find that nicotinamide promotes survival differentiation human pluripotent cells. Nicotinamide inhibits phosphorylation myosin light chain, suppresses actomyosin contraction, leads improved after individualization. Further analysis demonstrates an inhibitor multiple kinases,...
Abstract Epstein-Barr virus (EBV) is a significant epigenetic driver in the development of epithelial-origin nasopharyngeal carcinoma (NPC) and gastric cancer (GC), which together represent 80% EBV-associated malignancies. Despite its known association, specific mechanisms, particularly those involving EBV-induced histone modifications, remain poorly understood. Through integrative analyses single-cell bulk transcriptome data from epithelial tumor tissues EBV-infected cells, we identified...
Nuclear factor κB (NF-κB) regulates gene expression by binding to specific DNA elements, known collectively as sites, that are contained within the promoters/enhancers of target genes. We found identity central base pair (bp) sites profoundly affects transcriptional activity NF-κB dimers. RelA dimers prefer an A/T bp at this position for optimal activation (A/T-centric) and discriminate against G/C-centric sites. The p52 homodimer, in contrast, activates transcription from complex with Bcl3...
The dimeric nuclear factor kappa B (NF-κB) transcription factors (TFs) regulate gene expression by binding to a variety of κB DNA elements with conserved G:C-rich flanking sequences enclosing degenerate central region. Toward defining mechanistic principles affinity regulated degeneracy, we observed an unusual dependence the RelA on identity base pair, which appears be noncontacted in complex crystal structures. sites A or T at position is ~10-fold higher than G C. structures neither...
Abstract Nasopharyngeal carcinoma (NPC) is an Asia‐prevalent malignancy, yet its genetic underpinnings remain incompletely understood. Here, a transcriptome‐wide association study (TWAS) conducted on NPC, leveraging gene expression prediction models based epithelial tissues and genome‐wide (GWAS) summary statistics from 1577 NPC cases 6359 controls of southern Chinese descent. The TWAS identifies VAMP8 chromosome 2p11.2 as novel susceptibility for NPC. Further fine‐mapping analyses pinpoint...
The DXO family of proteins participates in eukaryotic mRNA 5'-end quality control, removal non-canonical NAD+ cap and maturation fungal rRNA precursors. In this work, we characterize the Arabidopsis thaliana homolog, DXO1. We demonstrate that plant-specific modification within active site negatively affects capping surveillance properties DXO1, but has only a minor impact on its strong deNADding activity. Unexpectedly, catalytic activity does not contribute to striking morphological...
Coronavirus disease 2019 , caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has a global pandemic.Intermediate horseshoe bats (Rhinolophus affinis) are hosts of RaTG13, the second most phylogenetically related viruses to SARS-CoV-2.We report binding between intermediate bat ACE2 (bACE2-Ra) and SARS-CoV-2 receptor-binding domain (RBD), supporting pseudotyped viral infection.A 3.3 Å resolution crystal structure bACE2-Ra/SARS-CoV-2 RBD complex was determined.The...
The mammalian NF-κB p52:p52 homodimer together with its cofactor Bcl3 activates transcription of κB sites a central G/C base pair (bp), while it is inactive toward A/T bp. To understand the molecular basis for this unique property p52, we have determined crystal structures recombinant human p52 protein in complex P-selectin(PSel)-κB DNA (5′-GGGGT G ACCCC-3′) (central bp underlined) and variants changing to or swapping flanking reveal nearly two-fold widened minor groove region as compared...
The NF-κB subunit RelB determines whether inhibitory or transcriptionally active complexes are formed during noncanonical signaling.
Transcription activator proteins typically contain two functional domains: a DNA binding domain (DBD) that binds to with sequence specificity and an activation (AD) whose established function is recruit RNA polymerase. In this report, we show purified recombinant nuclear factor κB (NF-κB) RelA dimers bind specific sites affinity significantly lower than of the same from extracts activated cells, suggesting additional cofactors might facilitate by dimers. Additionally, relatively low at...
The NF-κB family of dimeric transcription factors regulate diverse biological functions. Their cellular expression profiles differ, which lead to different concentrations in cell/tissue types. Although the activation mechanisms dimers have been widely investigated, there is limited information on specific dimers' formation. p52:p52 homodimer regulates an important subset target genes cancer cells; however, molecular mechanism generation this remains unclear. Our study has revealed that...
Abstract B cell lymphoma 3 (Bcl3), a member of the IκB family proteins, modulates transcription by primarily associating with NF-κB p50 and p52 homodimers. Bcl3 undergoes extensive phosphorylation, though functions many these modifications remain unclear. We previously described that phosphorylation at Ser33, Ser114 Ser446 partially switches from acting as an IκB-like inhibitor to regulator (p52:p52):DNA binary complex. Here, we identified another critical site, Ser366. Substituting all four...