A5013308419- FOXO transcription factor regulation
- Autophagy in Disease and Therapy
- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- Signaling Pathways in Disease
- RNA modifications and cancer
- PI3K/AKT/mTOR signaling in cancer
- Cell death mechanisms and regulation
- Cancer-related gene regulation
- Endoplasmic Reticulum Stress and Disease
- Histone Deacetylase Inhibitors Research
- Genetics, Aging, and Longevity in Model Organisms
- PARP inhibition in cancer therapy
- Mitochondrial Function and Pathology
- DNA Repair Mechanisms
- Cancer, Hypoxia, and Metabolism
- Genomics, phytochemicals, and oxidative stress
- Hippo pathway signaling and YAP/TAZ
- Parkinson's Disease Mechanisms and Treatments
- Neuroblastoma Research and Treatments
- Advanced Breast Cancer Therapies
- Renal cell carcinoma treatment
- Sirtuins and Resveratrol in Medicine
- RNA regulation and disease
- Protein Tyrosine Phosphatases
Xiamen University
2012-2025
Princess Margaret Cancer Centre
2017
Toxicologie, Pharmacologie et Signalisation Cellulaire
2017
University Health Network
2004-2012
Ontario Institute for Cancer Research
2012
University of Toronto
2004-2008
University of Ulsan
2006
Asan Medical Center
2006
Ulsan College
2006
Rutgers Cancer Institute of New Jersey
2006
Although aerobic glycolysis (the Warburg effect) is a hallmark of cancer, key questions, including when, how, and why cancer cells become highly glycolytic, remain less clear. For largely unknown regulatory mechanism, rate-limiting glycolytic enzyme pyruvate kinase M2 (PKM2) isoform exclusively expressed in embryonic, proliferating, tumor cells, plays an essential role metabolism growth. Because the receptor tyrosine kinase/PI3K/AKT/mammalian target rapamycin (RTK/PI3K/AKT/mTOR) signaling...
Puma is an essential mediator of p53-dependent and -independent apoptosis in vivo. In response to genotoxic stress, induced a manner. However, the transcription factor driving up-regulation p53-independent apoptotic stimuli has yet be identified. Here, we show that FOXO3a up-regulates expression cytokine or growth deprivation. Importantly, dysregulated Akt signaling lymphoid cells attenuated induction upon withdrawal. Our results suggest Puma, together with another BH3 only member, Bim,...
Abstract Reactive oxygen species (ROS) production in phagocytes is a major defense mechanism against pathogens. However, the cellular self-protective such potential damage from oxidative stress remains unclear. Here we show that kinases Mst1 and Mst2 (Mst1/2) sense ROS maintain redox balance by modulating stability of antioxidant transcription factor Nrf2. Site-specific release recruits Mst1/2 cytosol to phagosomal or mitochondrial membrane, with subsequently activating phosphorylate kelch...
Loss-of-function mutations of phosphatase/tensin homolog deleted on chromosome 10 (PTEN)-induced putative kinase 1 (Pink1) (also known as Park6) identified in familial forms Parkinson's disease (PD) are associated with compromised mitochondrial function. Emerging data suggest that Pink1 is an essential pro-survival factor induced response to oxidative stress. However, the mechanisms regulating expression under stress conditions remain unknown. Forkhead box, subgroup O (FOXO) transcription...
Abstract p53 is a transcription factor that implicated in the control of both apoptotic and autophagic cell death. This tumor suppressor elicits pro-autophagic anti-autophagic phenotypes depending its intracellular localization. The ability to repress autophagy has been exclusively associated cytoplasmic Here, we show transcriptional activity also contributes down-regulation. Thus, nuclear controls PINK1, key protein involved mitophagy, by repressing promoter activity, mRNA levels, ex-vivo...
FoxO transcription factors have been reported to play pivotal roles in tumorigenesis and drug resistance. The mechanisms underlying the tumor suppression function of FoxOs human cancers remain largely unknown. Aberrant expression activation Nrf2 often correlate with chemoresistance poor prognosis. Here, we report that FoxO3 directs basal Kelch‐like ECH‐associated protein 1 (Keap1), an adaptor bridges Cul3 for degradation. depletion resulted Keap1 down‐regulation, thereby activating...
Abstract The methyltransferase like 3 (METTL3) has been generally recognized as a nuclear protein bearing oncogenic properties. We find predominantly cytoplasmic METTL3 expression inversely correlates with node metastasis in human cancers. It remains unclear if is functionally distinct from cytosolic driving tumorigenesis and, any, how tumor cells sense insults to coordinate functions within these intracellular compartments. Here, we report an acetylation-dependent regulation of localization...
The tumor suppressor p53 can trigger cell death independently of its transcriptional activity through subcellular translocation and activation proapoptotic Bcl-2 family members. regulation such endogenous in response to stress remains largely unknown. Here we show that nuclear, activated FOXO3a could impair activity. However, either on serum starvation or by expressing a constitutively active form induce p53-dependent apoptosis, even cells bearing transcriptionally inactive p53. Furthermore,...
FKHRL1 (FOXO3a) and p53 are two potent stress-response regulators. Here we show that these transcription factors exhibit "crosstalk" in vivo. In response to DNA damage, activation led phosphorylation subcellular localization change, which resulted inhibition of activity. AKT was dispensable for p53-dependent suppression FKHRL1. By contrast, serum- glucocorticoid-inducible kinase 1 (SGK1) significantly induced a manner after this induction through extracellular signal-regulated 1/2-mediated...
Genomic amplification of OTUD7B is frequently found across human cancers. But its role in tumorigenesis poorly understood. Lysine-specific demethylase 1 (LSD1) known to execute epigenetic regulation by forming corepressor complex with CoREST/histone deacetylases (HDACs). However, the molecular mechanisms which cells maintain LSD1/CoREST integrity are unknown. Here, it reported that LSD1 protein undergoes K63-linked polyubiquitination. responsible for deubiquitination at K226/277 residues,...
Abstract Lacking a clear understanding of the molecular mechanism determining cancer cell sensitivity to oxidative phosphorylation (OXPHOS) inhibition limits development OXPHOS‐targeting treatment. Here, lines sensitive or resistant OXPHOS are identified by screening. inhibition‐sensitive cells possess increased activity and silenced nicotinamide N ‐methyltransferase (NNMT) expression. NNMT expression negatively correlates with functionally downregulates intracellular levels S‐adenosyl...
Autophagy is a potentially inimical pathway and together with apoptosis, may be activated by similar stress stimuli that can lead to cell death. The molecular cues dictate the fate choice between autophagy apoptosis remain largely unknown. Here we report proapoptotic protein BBC3/PUMA (BCL2 binding component 3) bona fide substrate of chaperone-mediated (CMA). BBC3 associates HSPA8/HSC70 (heat shock 70kDa 8), leading its lysosome translocation uptake. Inhibition CMA results in stabilization...
Cellular homeostasis is controlled by pathways that balance cell death with survival. Mcl-1 ubiquitin ligase E3 (Mule) an targets the proapoptotic molecule p53 for polyubiquitination and degradation. To elucidate role of Mule in B lymphocyte homeostasis, cell–specific knockout (BMKO) mice were generated using Cre–LoxP recombination system. Analysis BMKO showed was essential development, proliferation, humoral immune responses. transactivation increased two- to fourfold Mule-deficient cells...
Significance Oncogenic hotspot mutations in PIK3CA or RAS and overexpression of Her2 are known as a driving force for human cancer development. We others have shown that ΔNp63α, the major protein isoform p53-related p63 expressed epithelial cells, functions an important regulator cell adhesion program is critical inhibitor metastasis. In this study, we demonstrate oncogenic p110α H1047R , K-Ras G12V H-Ras use common Akt1-FOXO3a pathway suppression ΔNp63α expression and, consequently, promote...
Geminin expression is essential for embryonic development and the maintenance of chromosomal integrity. In spite this protective role, geminin also frequently overexpressed in human cancers molecular mechanisms underlying its role tumor progression remain unclear. The histone deacetylase HDAC3 modulates transcription factors to activate or suppress transcription. Little known about how specifies substrates modulation among highly homologous factor family members. Here, we have demonstrated...
BackgroundMitophagy and mitochondrial dynamics alterations are two major hallmarks of neurodegenerative diseases. Dysfunctional mitochondria accumulate in Alzheimer's disease–affected brains by yet unexplained mechanisms.MethodsWe combined cell biology, molecular pharmacological approaches to unravel a novel pathway which presenilins control phosphatase tensin homolog–induced kinase 1 (Pink-1) expression transcription. In vivo were carried out on various transgenic knockout animals as well...
Parkinson disease (PD)-affected brains show consistent endoplasmic reticulum (ER) stress and mitophagic dysfunctions. The mechanisms underlying these perturbations how they are directly linked remain a matter of questions. XBP1 is transcription factor activated upon ER after unconventional splicing by the nuclease ERN1/IREα thereby yielding XBP1s, whereas PINK1 kinase considered as sensor mitochondrial physiology master gatekeeper mitophagy process. We showed that XBP1s transactivates in...