A5068511869- Retinoids in leukemia and cellular processes
- bioluminescence and chemiluminescence research
- Biotin and Related Studies
- Protein Degradation and Inhibitors
- Click Chemistry and Applications
- Alkaline Phosphatase Research Studies
- RNA Interference and Gene Delivery
- interferon and immune responses
- Acute Myeloid Leukemia Research
- Ubiquitin and proteasome pathways
- Virus-based gene therapy research
- Histone Deacetylase Inhibitors Research
- GaN-based semiconductor devices and materials
- Cancer-related Molecular Pathways
- Cancer Cells and Metastasis
- Ultrasound and Hyperthermia Applications
- Advanced Breast Cancer Therapies
- Cancer-related cognitive impairment studies
- Advanced biosensing and bioanalysis techniques
Zhejiang University
2020-2025
First Affiliated Hospital Zhejiang University
2020-2024
Zhejiang Lab
2021
Hangzhou Xixi hospital
2020
Abstract PML nuclear bodies (NB) are disrupted in PML-RARA–driven acute promyelocytic leukemia (APL). Arsenic trioxide (ATO) cures 70% of patients with APL, driving PML-RARA degradation and NB reformation. In non-APL cells, arsenic binding onto also amplifies formation. Yet, the actual molecular mechanism(s) involved remain(s) elusive. Here, we establish that NBs display some features liquid–liquid phase separation ATO induces a gel-like transition. B-box-2 structure reveals an alpha helix...
The PML/RARα fusion protein is the oncogenic driver in acute promyelocytic leukemia (APL). Although most APL cases are cured by PML/RARα-targeting therapy, relapse and resistance can occur due to drug-resistant mutations. Here we report that thermal stress destabilizes protein, including clinically identified mutants. AML1/ETO TEL/AML1 oncofusions show similar heat shock susceptibility. Mechanistically, mild hyperthermia stimulates aggregation of complex with nuclear receptor corepressors...
CD133 targeted aptamer–drug conjugates could precisely deliver anti-cancer drugs into positive anaplastic thyroid cancer tissue.
<div>Abstract<p>PML nuclear bodies (NB) are disrupted in PML-RARA–driven acute promyelocytic leukemia (APL). Arsenic trioxide (ATO) cures 70% of patients with APL, driving PML-RARA degradation and NB reformation. In non-APL cells, arsenic binding onto PML also amplifies formation. Yet, the actual molecular mechanism(s) involved remain(s) elusive. Here, we establish that NBs display some features liquid–liquid phase separation ATO induces a gel-like transition. B-box-2 structure...
<div>Abstract<p>PML nuclear bodies (NB) are disrupted in PML-RARA–driven acute promyelocytic leukemia (APL). Arsenic trioxide (ATO) cures 70% of patients with APL, driving PML-RARA degradation and NB reformation. In non-APL cells, arsenic binding onto PML also amplifies formation. Yet, the actual molecular mechanism(s) involved remain(s) elusive. Here, we establish that NBs display some features liquid–liquid phase separation ATO induces a gel-like transition. B-box-2 structure...
<p>Figure S3 shows that PML B2 trimer controls NB distribution and dynamics ranging from a liquid-like bodies to filaments</p>
<p>Figure S1 illustrates LLPS hallmarks of PML nuclear bodies and highlights that their assembly does not rely on intermolecular disulfide bonds</p>
<p>Figure S4 illustrates how trivalent arsenic binding to C213 in the B2 trimer leads PML NB aggregation, and defective sumoylation degradation of mutants, as well role mutants on partner localization sumoylation</p>
<p>Figure S2 shows Crystal structure of MBP-B2 fusion protein, and the similarity between 3D PML B2 other TRIM proteins, yet its formation relies on specific amino acids</p>
<p>Figure S1 illustrates LLPS hallmarks of PML nuclear bodies and highlights that their assembly does not rely on intermolecular disulfide bonds</p>
<p>Figure S2 shows Crystal structure of MBP-B2 fusion protein, and the similarity between 3D PML B2 other TRIM proteins, yet its formation relies on specific amino acids</p>
<p>Figure S4 illustrates how trivalent arsenic binding to C213 in the B2 trimer leads PML NB aggregation, and defective sumoylation degradation of mutants, as well role mutants on partner localization sumoylation</p>
<p>Figure S3 shows that PML B2 trimer controls NB distribution and dynamics ranging from a liquid-like bodies to filaments</p>
<p>Supplementary movie 2 shows Incomplete PML NBs fusion upon ATO treatment (1µM, 1h) in MEFs</p>
<p>Supplementary movie 2 shows Incomplete PML NBs fusion upon ATO treatment (1µM, 1h) in MEFs</p>
<p>Figure S5 displays how B2 trimer is essential for PML-RARA microspeckle formation in progenitors and PML NB disruption as well PML/RARA degradation ex vivo, sumoylation vivo</p>