A5079847742- Cholesterol and Lipid Metabolism
- Cancer, Lipids, and Metabolism
- RNA modifications and cancer
- Peroxisome Proliferator-Activated Receptors
- Hepatitis B Virus Studies
- Cell death mechanisms and regulation
- Cancer, Hypoxia, and Metabolism
- Atherosclerosis and Cardiovascular Diseases
- Cancer, Stress, Anesthesia, and Immune Response
- Ferroptosis and cancer prognosis
- Immune cells in cancer
- Ubiquitin and proteasome pathways
- RNA Research and Splicing
- Metabolism, Diabetes, and Cancer
- Cancer-related Molecular Pathways
- Chemokine receptors and signaling
- Lipid metabolism and biosynthesis
- Plant biochemistry and biosynthesis
Zhongnan Hospital of Wuhan University
2023-2024
Wuhan University
2023-2024
Abstract Mitochondrial apoptosis is strictly controlled by BCL-2 family proteins through a subtle network of protein interactions. The tumor suppressor p53 triggers transcription-independent direct interactions with proteins, but the molecular mechanism not well understood. In this study, we present three crystal structures p53-DBD in complex anti-apoptotic at resolutions 2.3–2.7 Å. show that two loops penetrate directly into BH3-binding pocket BCL-2. Structure-based mutations interface...
Abstract Tumor cells reprogram their metabolism to produce specialized metabolites that both fuel own growth and license tumor immune evasion. However, the relationships between these functions remain poorly understood. Here, we report CRISPR screens in a mouse model of colo-rectal cancer (CRC) implicates dual specificity phosphatase 18 (DUSP18) establishment tumor-directed Dusp18 inhibition reduces CRC rates, which correlate with high levels CD8 + T cell activation. Mechanistically, DUSP18...
Abstract The metabolic pathways through which p53 functions as a potent tumor suppressor are incompletely understood. Here we report that, by associating with the Vitamin D receptor (VDR), induces numerous genes encoding enzymes for peroxisomal fatty acid β-oxidation (FAO). This leads to increased cytosolic acetyl-CoA levels and acetylation of enzyme 5-Aminoimidazole-4-Carboxamide Ribonucleotide Formyltransferase/IMP Cyclohydrolase (ATIC), catalyzes last two steps in purine biosynthetic...
Cholesterol metabolism reprogramming plays essential roles in hepatocellular carcinoma (HCC). However, precisely how cholesterol is dysregulated not clear. Here, we show that the palmitoyltransferase ZDHHC3 and depalmitoylase ABHD17A regulate HCC cell biosynthesis by dynamically S-acylating SREBP cleavage-activating protein (SCAP). SCAP S-acylation at C264 antagonizes HACE1-mediated ubiquitination. Intriguingly, SREBP2 transcriptionally upregulates to form a positive feedback loop, which...
β-catenin signaling is abnormally activated in cancer. Here, this work screens the mevalonate metabolic pathway enzyme PMVK to stabilize using a human genome-wide library. On one hand, PMVK-produced MVA-5PP competitively binds CKIα prevent Ser45 phosphorylation and degradation. other functions as protein kinase directly phosphorylate Ser184 increase its nuclear localization. This synergistic effect of together promotes signaling. In addition, deletion impairs mouse embryonic development...
Abstract Certain metabolites in the tumor microenvironment (TME) can alter innate immunity. Here, it is shown how phosphomevalonate kinase (PMVK) allows hepatocellular carcinoma (HCC) cells to overcome anti‐tumor immunity mediated by CD8 + T cells. In HCCs, depletion of PMVK required facilitate cell activation and their subsequent suppression growth. Mechanistically, phosphorylates stabilizes glutamate decarboxylase 1 (GAD1), thus increasing synthesis γ‐aminobutyric acid (GABA), which...
Many human cancers carry missense mutations in or deletions of the tumor protein 53 (TP53) suppressor gene. TP53's product, p53 regulates many biological processes, including cell metabolism. Cholesterol is a key lipid needed for maintenance membrane function and tissue homeostasis while also serving as precursor steroid hormone bile acid synthesis. An over-abundance cholesterol can lead to its esterification storage esters. The recent study has shown that loss leads excessive ester...