A5019190678- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- Enzyme Structure and Function
- Protein Degradation and Inhibitors
- RNA modifications and cancer
- Injury Epidemiology and Prevention
- HIV Research and Treatment
- PARP inhibition in cancer therapy
- Protein Structure and Dynamics
- Burn Injury Management and Outcomes
- Immune Cell Function and Interaction
- RNA Research and Splicing
- Adipose Tissue and Metabolism
- Plant Stress Responses and Tolerance
- Biochemical and Molecular Research
- Hepatitis C virus research
- bioluminescence and chemiluminescence research
- Regulation of Appetite and Obesity
- DNA Repair Mechanisms
- 14-3-3 protein interactions
- Autophagy in Disease and Therapy
- Chemical Synthesis and Analysis
- Computational Drug Discovery Methods
- interferon and immune responses
- Wound Healing and Treatments
The University of Texas MD Anderson Cancer Center
2015-2024
Wuhan University
2010-2017
Indiana University – Purdue University Indianapolis
2013
Indiana University School of Medicine
2013
Shanghai Institute of Hematology
2000
Chinese National Human Genome Center
2000
Fudan University
2000
Moredun Research Institute
1995
PRMT5 is an arginine methyltransferase that accounts for the vast majority of symmetric methylation in cells. exerts its function when complexed with MEP50/WDR77. This activity often elevated cancer cells and correlates poor prognosis, making a therapeutic target. To investigate signaling pathway to identify genes whose loss-of-function sensitizes inhibition, we performed CRISPR/Cas9 genetic screen presence inhibitor. We identified known components writer/reader including itself,...
The aberrant expression of protein arginine methyltransferase 5 (PRMT5) has been associated with multiple cancers. Using the proteolysis targeting chimera technology, we discovered a first-in-class PRMT5 degrader 15 (MS4322). Here, report design, synthesis, and characterization compound two structurally similar controls 17 (MS4370) 21 (MS4369), impaired binding to von Hippel-Lindau E3 ligase PRMT5, respectively. Compound 15, but not 21, effectively reduced level in MCF-7 cells. Our mechanism...
Abstract The coactivator associated arginine methyltransferase (CARM1) promotes transcription, as its name implies. It does so by modifying histones and chromatin bound proteins. We identified nuclear factor I B (NFIB) a CARM1 substrate show that this transcription utilizes coactivator. Biochemical studies reveal tripartite motif 29 (TRIM29) is an effector molecule for methylated NFIB. Importantly, NFIB harbors both oncogenic metastatic activities, often overexpressed in small cell lung...
Coronaviruses possess a cap structure at the 5' ends of viral genomic RNA and subgenomic RNAs, which is generated through consecutive methylations by virally encoded guanine-N7-methyltransferase (N7-MTase) 2'-O-methyltransferase (2'-O-MTase). The coronaviral N7-MTase unique for its physical linkage with an exoribonuclease (ExoN) harbored in nonstructural protein 14 (nsp14) coronaviruses. In this study, structure-function relationships were analyzed deletion site-directed mutagenesis severe...
The type II arginine methyltransferase PRMT5 is responsible for the symmetric dimethylation of histone to generate H3R8me2s and H4R3me2s marks, which correlate with repression transcription. However, protein level a number genes (MEP50, CCND1, MYC, HIF1a, MTIF CDKN1B) are reported be downregulated by loss PRMT5, while their mRNA levels remain unchanged, counterintuitive PRMT5's proposed role as transcription repressor. We noticed that majority regulated at posttranscriptional level, express...
The primary neuroendocrine interface, hypothalamus and pituitary, together with adrenals, constitute the major axis responsible for maintenance of homeostasis response to perturbations in environment. gene expression profiling human hypothalamus-pituitary-adrenal was catalogued by generating a large amount expressed sequence tags (ESTs), followed bioinformatics analysis ( http://www.chgc.sh.cn/ database). Totally, 25,973 sequences good quality were obtained from 31,130 clones (83.4%) cDNA...
CARM1 is a protein arginine methyltransferase (PRMT) that acts as coactivator in number of transcriptional programs. orchestrates this activity part by depositing the H3R17me2a histone mark vicinity gene promoters it regulates. However, gross levels KO mice did not significantly decrease, indicating other PRMT(s) may compensate for loss. We thus performed screen type I PRMTs, which revealed PRMT6 can also deposit vitro. knockout are perinatally lethal and display reduced fetal size, whereas...
ABSTRACT Hepatitis B virus (HBV), a small enveloped DNA virus, chronically infects more than 350 million people worldwide and causes liver diseases from hepatitis to cirrhosis cancer. Here, we report that hepatocyte nuclear factor 6 (HNF6), liver-enriched transcription factor, can inhibit HBV gene expression replication. Overexpression of HNF6 inhibited, while knockdown enhanced, replication in hepatoma cells. Mechanistically, the SP2 promoter was inhibited by HNF6, which partly accounts for...
PRMT5 is the primary enzyme responsible for deposition of symmetric dimethylarginine in mammalian cells. In an effort to understand how regulated, we identified a threonine phosphorylation site within C-terminal tail motif, which targeted by Akt/serum- and glucocorticoid-inducible kinases. While investigating function this posttranslational modification, serendipitously discovered that its free binds PDZ domains (when unphosphorylated) 14-3-3 proteins phosphorylated). essence, event last few...
Abstract SPINDOC is tightly associated with the histone H3K4me3 effector protein SPIN1. To gain a better understanding of biological roles SPINDOC, we identified its interacting proteins. Unexpectedly, forms two mutually exclusive complexes, one SPIN1 and other PARP1. Consistent ability to directly interact PARP1, expression induced by DNA damage, likely KLF4, recruited lesions dynamics that follows In knockout cells, levels PARylation are reduced, in both absence presence damage. The...
A variety of cellular factors participates in the HIV-1 life cycle. Among them is well characterized cyclin T1 (CYCT1). CycT1 binds to cyclin-dependent kinase 9 (CDK9) and forms positive transcription elongation factor-b (P-TEFb). P-TEFb then recruited by TAT long terminal repeat (LTR) promoter subsequently leads phosphorylation C-terminal domain RNA polymerase II (pol II), enhanced processivity pol II, a full-length RNA. In this study, we report identification new CYCT1 splice variant,...
Abstract Protein arginine methylation is a common post-translational modification (PTM) catalyzed by nine protein methyltransferases (PRMTs). As the major symmetric methyltransferase that methylates both histone and non-histone substrates, PRMT5 plays key roles in number of biological processes critical for development tumorigenesis. overexpression has been reported multiple cancer types including prostate (PCa), but exact mechanistic understanding aggressive PCa remains ill-defined. Here,...
ABSTRACT Positive transcription elongation factor‐b (P‐TEFb) is required for the release of RNA polymerase II (RNAPII) from its pause near gene promoters and thus efficient proceeding to elongation. It consists two core subunits—CDK9 one T‐typed or K‐typed cyclin, which, cyclin T1/CDK9 major most studied combination. We have previously identified a novel splice variant T1, T1b, which negatively regulates HIV‐1 genes as well several host genes. In this study, we revealed serine‐arginine‐rich...
Protein arginine methylation is a common post-translational modification (PTM) catalyzed by nine protein methyltransferases (PRMTs). As the major symmetric methyltransferase that methylates both histone and non-histone substrates, PRMT5 plays key roles in number of biological processes critical for development tumorigenesis. overexpression has been reported multiple cancer types including prostate (PCa), but exact mechanistic understanding aggressive PCa remains ill-defined. Here, we show...