A5015917699- Ubiquitin and proteasome pathways
- Cancer-related Molecular Pathways
- Autophagy in Disease and Therapy
- RNA modifications and cancer
- PI3K/AKT/mTOR signaling in cancer
- Protein Degradation and Inhibitors
- Cancer, Hypoxia, and Metabolism
- Microbial Metabolic Engineering and Bioproduction
- Coenzyme Q10 studies and effects
- Peptidase Inhibition and Analysis
- Histone Deacetylase Inhibitors Research
- ATP Synthase and ATPases Research
- Cancer-related gene regulation
- DNA Repair Mechanisms
- Cancer, Lipids, and Metabolism
- Hippo pathway signaling and YAP/TAZ
- Endoplasmic Reticulum Stress and Disease
- Epigenetics and DNA Methylation
- Microtubule and mitosis dynamics
- Mitochondrial Function and Pathology
- Bone Tissue Engineering Materials
- Biochemical Acid Research Studies
- Genetics and Neurodevelopmental Disorders
- Cell death mechanisms and regulation
- PARP inhibition in cancer therapy
Zhejiang University
2016-2025
Second Affiliated Hospital of Zhejiang University
2018-2025
Ministry of Education of the People's Republic of China
2025
Northwest A&F University
2023
Cancer Institute (WIA)
2022
First Affiliated Hospital Zhejiang University
2018
University of Michigan
2009-2018
Michigan United
2018
New York Blood Center
2012
Peking University
2011
MLN4924, a newly discovered small molecule inhibitor of NEDD8-activating enzyme (NAE), inactivates Cullin-RING E3 ubiquitin Ligases (CRLs) by blocking cullin neddylation. As result, MLN4924 causes accumulation several key substrates CRLs and effectively suppresses tumor cell growth inducing apoptosis senescence. However, the role in induction autophagy its biological significance are totally unknown. Here we showed that induces both time- dose-dependent manners multiple human cancer lines,...
Abstract FBXW2 inhibits proliferation of lung cancer cells by targeting SKP2 for degradation. Whether and how regulates tumor invasion metastasis is previously unknown. Here, we report that an E3 ligase β-catenin. binds to β-catenin upon EGF-AKT1-mediated phosphorylation on Ser 552 , promotes its ubiquitylation overexpression reduces levels protein half-life, whereas knockdown increases levels, half-life transcriptional activity. Functionally, migration blocking transactivation MMPs driven...
SOX2 is a key transcription factor that plays critical roles in maintaining stem cell property and conferring drug resistance. However, the underlying mechanisms by which level precisely regulated remain elusive. Here we report MLN4924, also known as pevonedistat, small-molecule inhibitor of neddylation currently phase II clinical trials, down-regulates expression via causing accumulation MSX2, repressor expression. Mechanistic characterization revealed MSX2 substrate FBXW2 E3 ligase. binds...
Abstract p53 is regulated at multiple levels. We report here that p53, in lines of human cancer cells, down-regulated by cardiac glycoside drugs digoxin and ouabain, potent inhibitors Na+/K+-ATPase. These reduced the basal levels protein nanomolar concentrations a dose-, time-, cell line–dependent manner, but independent status wild-type or mutant. The also induced its activators as well transfected into regardless status. Interestingly, had no effect on endogenous two immortalized lines....
Significance FBXW7 is a typical tumor suppressor by targeting many oncoproteins for ubiquitylation and degradation, whereas LSD1 has oncogenic activity. Whether how interact, with what biological consequence, are unknown. Here, we report that pseudosubstrate of FBXW7. Upon binding FBXW7, LSD1, instead being degraded, disrupts dimerization promotes self-ubiquitylation degradation via proteasome lysosomal pathways in manner independent its demethylase As such, abrogates functions growth...
Abstract β-TrCP and SKP2 are two well-studied F-box proteins, which often act as oncogenes. Whether how they communicate with each other is unknown. Here we report that FBXW2, a poorly characterized F-box, substrate of β-TrCP1 an E3 ligase for SKP2. While promotes FBXW2 ubiquitylation shortens its half-life, does the same to has tumour suppressor activity against lung cancer cells blocks oncogenic function both The levels β-TrCP1-FBXW2-SKP2 inversely correlated during cell cycle β-TrCP/SKP2...
The tumor suppressor p53 plays a critical role in integrating wide variety of stress responses. Therefore, levels are precisely regulated by multiple ubiquitin ligases. In this study, we report that FBXW7, substrate recognition component the SKP1-CUL1-F-box (SCF) E3 ligase, interacts with and targets for polyubiquitination proteasomal degradation after exposure to ionizing radiation or etoposide. Mechanistically, DNA damage activates ATM phosphorylate on Ser33 Ser37, which facilitates FBXW7...
Ubiquitin-conjugating enzyme E2C (UBE2C) mediates ubiquitylation chain formation via the K11 linkage. While previous in vitro studies showed that UBE2C plays a growth-promoting role cancer cell lines, underlying mechanism remains elusive. Still unknown is whether and how promoting vivo. Here we report was indeed essential for growth survival of lung cells harboring Kras mutations, required KrasG12D-induced tumorigenesis, since Ube2c deletion significantly inhibited tumor extended lifespan...
Abstract Protein neddylation is catalyzed by a activating enzyme (NAE, E1), an E2 conjugating enzyme, and E3 ligase. In various types of human cancers, the pathway abnormally activated. Our previous study validated that UBE2F promising therapeutic target in lung cancer. Although NAE inhibitor MLN4924/pevonedistat currently under clinical investigation as anti-cancer agent, there are no small molecules available selectively UBE2F. Here, we report, for first time, discovery, via...
Sensitive to apoptosis gene (SAG; also known as RBX2 or ROC2) was originally cloned a redox-inducible antioxidant protein and later characterized RING component of SCF E3 ubiquitin ligases. SAG overexpression inhibits induced by many stimuli both in vitro vivo. mRNA overexpressed human lung tumor tissues with correlation poor patient survival. To investigate whether serves an anticancer target, we determined the effect silencing on cell proliferation, survival, radiosensitivity.SAG...
FBXW7 is a tumor suppressive E3 ligase, whereas RAS-ERK and mechanistic target of rapamycin kinase (mTORC1) are two major oncogenic pathways. Whether how regulates these pathways unknown. Here, we showed that SHOC2, RAS activator, substrate. Growth stimuli trigger SHOC2 phosphorylation on Thr507 by the mitogen-activated protein (MAPK) signal, which facilitates binding for ubiquitylation degradation. FBXW7-mediated degradation terminates RAS-MAPK signals inhibits proliferation. Furthermore,...
Abstract MLN4924 is a first-in-class small molecule inhibitor of NEDD8-activating enzyme (NAE), which currently in several clinical trials for anti-cancer applications. However, also showed some off-target effects with potential to promote the growth cancer cells counteracts its anticancer activity. In this study, we found that increases levels PD-L1 mRNA and protein dose- time-dependent manners. Mechanistic study effect largely independent neddylation inactivation, but due activation both...
UBE2F, a neddylation E2, neddylates CUL5 to activate cullin-RING ligase-5, upon coupling with E3 RBX2/SAG. Whether and how UBE2F controls pancreatic tumorigenesis is previously unknown. Here, we showed that essential for the growth of human cancer cells KRAS mutation. In mouse Kras
NOXA protein, a pro-apoptotic member of the BCL2 (B-cell lymphoma 2) protein family, exhibits high affinity for binding to MCL1 (myeloid cell leukemia 1) and interacts with BCL2A1 2-related A1). These interactions release BIM (BCL2 like 11), triggering apoptosis. Furthermore, facilitates proteasome-mediated degradation, critical response various anti-cancer drugs extracellular stimuli, including UV (ultraviolet) irradiation. Additionally, during oncogenic RAS activation, induces autophagic...
Abstract RNA polymerase II‐associated protein 2 (RPAP2) plays a critical role in transcriptional regulation. However, little is known about whether and how RPAP2 regulates hepatocellular carcinoma (HCC) cell growth, the stability precisely maintained. Here it reported that high levels HCC tissues correlate with poor patient survival. depletion suppresses growth survival of cells. F‐box WD repeat domain‐containing 7 (FBXW7) targets for polyubiquitylation degradation after being...