Cell Biology
All Items
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Abstract:
Tumor metabolic rewiring supports malignant growth and can concurrently dampen antitumor immunity, yet how the tumor-intrinsic mevalonate (MVA) pathway enforces immune escape remains insufficiently defined. Here we show that genetic or pharmacologic disruption of the MVA pathway in tumor cells elicits a robust immune response, increasing intratumoral CD8⁺ T cell infiltration and effector function...
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Abstract:
The NLRP3 inflammasome is a key driver in inflammatory, infectious, metabolic, and neurodegenerative diseases. Although the NLRP3 inhibitor CRID3 (also known as MCC950) exhibits potent activity, it cannot inhibit several hyperactive NLRP3 mutations associated with autoinflammatory syndromes and has not progressed clinically, underscoring the need for the development of new NLRP3 inhibitors....
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Abstract:
Chromosome substitution strains (CSS) are critical tools for dissecting complex traits, although iterative breeding steps and intraspecific compatibility requirements limit conventional approaches. Here, we developed an optimized TEAM platform for chromosome replacement combing CRISPR/Cas9–mediated chromosome elimination with microcell-mediated chromosome transfer (MMCT). Using this approach, we...
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Abstract:
The mitochondrial unfolded protein response (UPRmt) is a critical mechanism for restoring cellular homeostasis and promoting longevity upon mitochondrial stress. However, the mechanisms that sense specific mitochondrial damage-associated signals and activate UPRmt remain largely unknown. Through a genome-wide RNAi screen in Caenorhabditis elegans, we identified the AT-hook protein LIN-15B as a...
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Abstract:
Transcription factors drive gene expression dysregulation in cancer. However, non-canonical oncogenic mechanisms of these factors are unclear. Utilizing function-centric proteomics to discover RNA-dependent protein-protein interactions, we uncovered an unexpected interaction between transcription factor oncogene SOX2 and methionine cycle enzyme AHCY. Immunofluorescence and CUT&RUN revealed...
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Abstract:
Cells must eliminate various unwanted organelles to maintain homeostasis, yet how they achieve this when their primary degradation system, the lysosome, is impaired remains poorly understood. Here, we discover cytopurgosis, a lysosome-independent organelle-removal pathway that expels multiple organelles, including entire lysosomes, within large extracellular vesicles that we termed "purgasomes"....
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Abstract: Background: Variants in the dynamin 1-like (DNM1L) gene, which encodes dynamin-related protein 1 (Drp1), can cause encephalopathy due to defective mitochondrial and peroxisomal fission 1 (EMPF1) and optic atrophy 5 (OPA5), two neurodevelopmental disorders with distinct symptoms. Given the critical role of Drp1 in mitochondrial fission, it is believed that disrupted mitochondrial fission is key to...
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Abstract:
Genome instability drives tumor evolution through incremental mutations and catastrophic events such as chromothripsis. Despite significant advances, the diversity and underlying mechanisms of genome instability remain insufficiently understood. Here, we identify a previously unrecognized form of genome instability termed "chromocytosis", in which chromosome bridge breakage during mitosis causes...
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Abstract:
SUN1/2, core components of the linker of nucleoskeleton and cytoskeleton (LINC) complex, transmit extracellular mechanical forces to nuclear lamina and chromatin. However, their role in regulating peripheral chromatin in mechanosensing and mechanoadaptation remains unclear. Using CRISPR/Cas9-mediated knockout of Sun1 or Sun2 in myoblasts, we identified a SUN1/2-dependent mechano-feedback loop....
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Matrix Stiffness Induces Midnolin-dependent Lamin B1 Degradation to Control Myoblast Differentiation
Abstract:Cells decode mechanical cues to direct fate decisions through nuclear remodeling, yet nuclear adaptors to mechanical signals remain elusive. Here, we show that soft matrix suppresses myoblast differentiation and induces nuclear abnormality within 30 minutes, accompanied by a >60% reduction in lamin B1 proteins levels. Mechanistically, midnolin interacts with lamin B1 and mediates...