A5103090557- Quinazolinone synthesis and applications
- DNA Repair Mechanisms
- Synthesis and Characterization of Heterocyclic Compounds
- Synthesis and biological activity
- Microtubule and mitosis dynamics
- Mitochondrial Function and Pathology
- Cancer therapeutics and mechanisms
- Synthesis and Biological Evaluation
- Ubiquitin and proteasome pathways
- Cancer-related Molecular Pathways
- RNA modifications and cancer
- Glycosylation and Glycoproteins Research
- Genetic Neurodegenerative Diseases
- Epigenetics and DNA Methylation
- PARP inhibition in cancer therapy
- TGF-β signaling in diseases
- Protein Tyrosine Phosphatases
- Cell Adhesion Molecules Research
- Cellular transport and secretion
- Cancer Genomics and Diagnostics
- Nerve injury and regeneration
- Galectins and Cancer Biology
- Cell death mechanisms and regulation
- ATP Synthase and ATPases Research
- Genetic factors in colorectal cancer
Capital Normal University
2010-2021
Shenzhen University Health Science Center
2019-2021
Shenzhen University
2016-2018
Houston Methodist
2012
National Institute of Biological Sciences, Beijing
2012
Methodist Hospital
2012
China Agricultural University
2012
Alexandria University
2012
State Key Laboratory of Cancer Biology
2009
National University of Singapore
2007
Proper DNA damage response is essential for the maintenance of genome integrity. The E3 ligase RNF168 deficiency fully prevents both initial recruitment and retention 53BP1 at sites damage. In to damage, RNF168-dependent lysine-specific demethylase LSD1 site promotes local H3K4me2 demethylation ubiquitination H2A/H2AX, facilitating Alternatively, RNF168-mediated K63-linked ubiquitylation required its function in repair. We demonstrated here that phosphorylation dephosphorylation S131 S137...
Abstract Polo-like kinase 1 (PLK1) is a master that regulates cell cycle progression. How its enzymatic activity regulated in response to DNA damage not fully understood. We show PLK1 enriched at double strand breaks (DSBs) within seconds of UV laser irradiation PARP-1-dependent manner and then disperses 10 min PARG-dependent manner. Poly(ADP-)ribose (PAR) chains directly bind vitro inhibit activity. CHK1-mediated phosphorylation S137 prevents binding PAR recruitment DSBs but ensures T210...
Nogo, MAG, and OMgp are myelin-associated proteins that bind to a neuronal Nogo-66 receptor (NgR/NgR1) limit axonal regeneration after central nervous system injury. Within Nogo-A, two separate domains known interact with NgR1. NgR1 is the founding member of three-member NgR family, whereas Nogo-A (RTN4A) belongs four-member reticulon family. Here, we systematically mapped interactions between these superfamilies, demonstrating novel nanomolar RTN2 RTN3 Because expressed in spinal cord white...
CLASPIN is an essential mediator in the DNA replication checkpoint, responsible for ATR (ataxia telangiectasia and Rad3-related protein)-dependent activation of CHK1 (checkpoint kinase 1). Here we found a dynamic signaling pathway that regulates turn over. Under unperturbed conditions, E3 ubiquitin ligase HERC2 stability deubiquitinating enzyme USP20 by promoting ubiquitination-mediated proteasomal degradation. stress, ATR-mediated phosphorylation results disassociation from USP20....
DNA double-strand breaks (DSBs) are among the most lethal lesions associated with genome stability which, when destabilized, predisposes organs to cancers. DSBs primarily fixed either little fidelity by non-homologous end joining (NHEJ) repair or high homology-directed (HDR). The phosphorylated form of H2AX on serine 139 (γ-H2AX) is a marker DSBs. In this study, we explored if protein phosphatase PP6 involved in DSB depletion its expression human cancer cell lines, and determined breast...
Reversible phosphorylation is an essential posttranslational modification to turn on/off a protein function and regulate many cellular activities, including DNA repair. A double-strand break (DSB) the most lethal form of damage mainly fixed by error-prone nonhomologous end joining (NHEJ)-mediated repair high-fidelity homology recombination (HR)-mediated We found previously that phosphatase PP4 required for HR-mediated DSB In this report, we showed depletion PP4C siRNA compromised...
MDC1 is a key mediator of the DNA-damage response in mammals with several phosphorylation-dependent protein interaction domains. The function its N-terminal forkhead-associated (FHA) domain remains elusive. Here, we show structural, biochemical and cellular data that FHA mediates dimerization to DNA damage. Crystal structures reveal face-to-face dimer pseudo-dyad symmetry. We found recognizes phosphothreonine 4 (pT4) at N-terminus determined crystal structure complex pT4 peptide. Biochemical...
Checkpoint kinase 1 (Chk1) is a instrumental for orchestrating DNA replication, damage checkpoints, the spindle assembly checkpoint, and cytokinesis. Despite Chk1's pivotal role in multiple cellular processes, many of its substrates remain elusive. Here, we identified O-linked β-N-acetylglucosamine (O-GlcNAc)-transferase (OGT) as one substrates. We found that Chk1 interacts with phosphorylates OGT at Ser-20, which not only stabilizes OGT, but also required Phospho-specific antibodies...
The combination of paclitaxel and doxorubicin is among the most successful chemotherapy regimens in cancer treatment. CDK5RAP2, when mutated, causes primary microcephaly. We show here that inhibition CDK5RAP2 expression chromosome mis-segregation, fails to maintain spindle checkpoint, associated with reduced checkpoint proteins BUBR1 MAD2 an increase chromatin-associated CDC20. resides on promoters regulates their transcription. Furthermore, CDK5RAP2-knockdown cells have increased resistance...
Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurologic disorder, whose symptoms include cerebellar and epilepsy. The disease caused by ATTCT expansion in the ATXN10 gene, which encodes Ataxin-10 protein. Here we identified polo-like kinase 1 (Plk1) as one of Ataxin-10's binding partners. We show that epitope-tagged Plk1 coimmunoprecipitate, phosphorylates at S77 T82 vitro. Knockdown with siRNA HeLa cells results cytokinesis defects-multinucleation, are rescued wild-type...
The association between the CHEK2 and breast cancer risk in Chinese women is unknown. Here, we screened full coding sequence 118 familial cases who are negative for mutations BRCA1 BRCA2, one recurrent mutation, c.1111C>T (p.H371Y), was identified five index this cohort. Functional analysis suggested that p.H371Y a pathogenic mutation resulted decreased kinase activity. We further 909 unselected 1,228 healthy individuals. frequencies of controls were 4.24% (5/118), 1.76% (16/909), 0.73%...
Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurologic disorder caused by ATTCT expansion in the ATXN10 gene. Previous investigations have identified that depletion of Ataxin-10, gene product, leads to cellular apoptosis and cytokinesis failure. Herein we identify mitotic kinase Aurora B as Ataxin-10 interacting partner. interacts with phosphorylates at S12, evidenced vitro mass spectrometry analysis. Both endogenous S12-phosphorylated localizes midbody during...