A5060110465- Hippo pathway signaling and YAP/TAZ
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Microtubule and mitosis dynamics
- RNA and protein synthesis mechanisms
- interferon and immune responses
- Cellular Mechanics and Interactions
- RNA modifications and cancer
- Enzyme Structure and Function
- DNA Repair Mechanisms
- NF-κB Signaling Pathways
- DNA and Nucleic Acid Chemistry
- Biochemical and Molecular Research
- Genetic Neurodegenerative Diseases
- Cell death mechanisms and regulation
- RNA regulation and disease
- Wnt/β-catenin signaling in development and cancer
- Ubiquitin and proteasome pathways
- Signaling Pathways in Disease
- Endoplasmic Reticulum Stress and Disease
- CRISPR and Genetic Engineering
- Cytokine Signaling Pathways and Interactions
- Cancer-related gene regulation
- Immune Response and Inflammation
- 14-3-3 protein interactions
Westlake University
2022-2025
The University of Texas Southwestern Medical Center
2004-2023
Chinese Academy of Sciences
2012-2021
Shanghai Institutes for Biological Sciences
2012-2021
Center for Excellence in Molecular Cell Science
2012-2021
University of Chinese Academy of Sciences
2017-2019
Tongji University
2014-2016
National Center of Neurology and Psychiatry
2011
Anhui University
2010
Cohesin is a chromosome-bound, multisubunit adenosine triphosphatase complex. After loading onto chromosomes, it generates loops to regulate chromosome functions. It has been suggested that cohesin organizes the genome through loop extrusion, but direct evidence lacking. Here, we used single-molecule imaging show recombinant human cohesin-NIPBL complex compacts both naked and nucleosome-bound DNA by extruding loops. compaction requires triphosphate (ATP) hydrolysis force sensitive. This...
As a ring-shaped adenosine triphosphatase (ATPase) machine, cohesin organizes the eukaryotic genome by extruding DNA loops and mediates sister chromatid cohesion topologically entrapping DNA. How executes these fundamental transactions is not understood. Using cryo-electron microscopy (cryo-EM), we determined structure of human bound to its loader NIPBL at medium resolution. Cohesin interact extensively together form central tunnel entrap 72-base pair promote engagement cohesin's ATPase head...
The mammalian STE20-like protein kinase 1 (MST1)-MOB activator (MOB1) complex has been shown to suppress the oncogenic activity of Yes-associated (YAP) in Hippo pathway, which is involved development multiple tumors, including pancreatic cancer (PC). However, it remains unclear whether other MST-MOB complexes are also regulating Hippo-YAP signaling and have potential roles PC. Here, we report that 4 (MST4), a distantly related ortholog MST1 kinase, forms with MOB4 phosphorylation-dependent...
Abstract Striatin-interacting phosphatases and kinases (STRIPAKs) are evolutionarily conserved supramolecular complexes, which have been implicated in the Hippo signaling pathway. Yet topological structure dynamic assembly of STRIPAK complexes remain elusive. Here, we report overall architecture substructures a kinase-containing complex. PP2Aa/c-bound STRN3 directly contacts kinase MST2 also controls loading via two “arms” phosphorylation-dependent manner, one arm being STRIP1 other...
Background and purpose: Mutations in the valosin‐containing protein ( VCP ) gene are known to cause inclusion body myopathy with Paget’s disease of bone frontotemporal dementia (IBMPFD) familial amyotrophic lateral sclerosis (ALS). Despite an increasing number clinical reports, only one Asian family IBMPFD has been described. Methods: To characterize patients mutations, we screened a total 152 unrelated families who were suspected have rimmed vacuolar myopathy. Results: We identified...
The protein phosphatase 2A (PP2A) and kinases such as germinal center kinase III (GCKIII) can interact with striatins to form a supramolecular complex called striatin-interacting (STRIPAK) complex. Despite the fact that STRIPAK regulates multiple cellular events, it remains only partially understood how this itself is assembled regulated for differential biological functions. Our recent work revealed activation mechanism of GCKIIIs by MO25, well heterodimerize CCM3, molecular bridge between...
The dynamic tyrosination-detyrosination cycle of α-tubulin regulates microtubule functions. Perturbation this impairs mitosis, neural physiology, and cardiomyocyte contraction. carboxypeptidases vasohibins 1 2 (VASH1 VASH2), in complex with the small vasohibin-binding protein (SVBP), mediate detyrosination. These enzymes detyrosinate microtubules more efficiently than soluble αβ-tubulin heterodimers. structural basis for substrate preference is not understood. Using cryo-electron microscopy...
The conserved ATPase p97 (Cdc48 in yeast) and adaptors mediate diverse cellular processes through unfolding polyubiquitinated proteins extracting them from macromolecular assemblies membranes for disaggregation degradation. tandem domains (D1 D2) of the p97/Cdc48 hexamer form stacked rings. can unfold substrates by threading central pore. pore loops critical substrate are, however, not well-ordered substrate-free conformations. How organizes its engagement is unclear. Here we show that...
Mammalian STE20-like kinase MST4 regulates multiple cellular aspects such as cell polarity and proliferation. acts downstream of LKB1/MO25/STRAD complex to induce brush border formation. MO25 directly interacts with promote its activity. Here, we report the crystal structure in MO25. Association rotates αC helix toward catalytic core, stabilizing an active position. The domain forms a specific homodimer that is required for trans-autophosphorylation. MO25-stimulated activation promotes...