p53 Suppresses Metabolic Stress-Induced Ferroptosis in Cancer Cells

Cell Reports, Journal Year: 2018, Volume and Issue: 22(3), P. 569 - 575

Published: Jan. 1, 2018

How cancer cells respond to nutrient deprivation remains poorly understood. In certain cells, of cystine induces a non-apoptotic, iron-dependent form cell death termed ferroptosis. Recent evidence suggests that ferroptosis sensitivity may be modulated by the stress-responsive transcription factor and canonical tumor suppressor protein p53. Using CRISPR/Cas9 genome editing, small-molecule probes, high-resolution, time-lapse imaging, we find stabilization wild-type p53 delays onset in response deprivation. This delay requires transcriptional target CDKN1A (encoding p21) is associated with both slower depletion intracellular glutathione reduced accumulation toxic lipid-reactive oxygen species (ROS). Thus, p53-p21 axis help cope metabolic stress induced delaying non-apoptotic death.

Language: Английский

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Small molecule metabolites: discovery of biomarkers and therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 20, 2023

Metabolic abnormalities lead to the dysfunction of metabolic pathways and metabolite accumulation or deficiency which is well-recognized hallmarks diseases. Metabolite signatures that have close proximity subject's phenotypic informative dimension, are useful for predicting diagnosis prognosis diseases as well monitoring treatments. The lack early biomarkers could poor serious outcomes. Therefore, noninvasive methods with high specificity selectivity desperately needed. Small molecule metabolites-based metabolomics has become a specialized tool biomarker pathway analysis, revealing possible mechanisms human various deciphering therapeutic potentials. It help identify functional related variation delineate biochemical changes indicators pathological damage prior disease development. Recently, scientists established large number profiles reveal underlying networks target exploration in biomedicine. This review summarized analysis on potential value small-molecule candidate metabolites clinical events, may better diagnosis, prognosis, drug screening treatment. We also discuss challenges need be addressed fuel next wave breakthroughs.

Language: Английский

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Cyclin D-Cdk4,6 Drives Cell-Cycle Progression via the Retinoblastoma Protein’s C-Terminal Helix

Molecular Cell, Journal Year: 2019, Volume and Issue: 74(4), P. 758 - 770.e4

Published: April 11, 2019

Language: Английский

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Cellular Control of Viscosity Counters Changes in Temperature and Energy Availability

Cell, Journal Year: 2020, Volume and Issue: 183(6), P. 1572 - 1585.e16

Published: Nov. 5, 2020

Language: Английский

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Structural insights into the functional roles of 14-3-3 proteins

Frontiers in Molecular Biosciences, Journal Year: 2022, Volume and Issue: 9

Published: Sept. 16, 2022

Signal transduction cascades efficiently transmit chemical and/or physical signals from the extracellular environment to intracellular compartments, thereby eliciting an appropriate cellular response. Most often, these signaling processes are mediated by specific protein-protein interactions involving hundreds of different receptors, enzymes, transcription factors, and signaling, adaptor scaffolding proteins. Among them, 14-3-3 proteins a family highly conserved molecules expressed in all eukaryotes, where they modulate function other proteins, primarily phosphorylation-dependent manner. Through binding interactions, participate key processes, such as cell-cycle control, apoptosis, signal transduction, energy metabolism, protein trafficking. To date, several partners have been identified, including kinases, phosphatases, receptors which implicated onset various diseases. As such, promising targets for pharmaceutical interventions. However, despite intensive research into their our understanding molecular mechanisms whereby regulate functions remains insufficient. This review article provides overview current state art partners, focusing on recent structural studies complexes.

Language: Английский

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RNA polymerase II dynamics and mRNA stability feedback scale mRNA amounts with cell size

Cell, Journal Year: 2023, Volume and Issue: 186(24), P. 5254 - 5268.e26

Published: Nov. 1, 2023

Language: Английский

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Frontiers of high-throughput metabolomics

Current Opinion in Chemical Biology, Journal Year: 2017, Volume and Issue: 36, P. 15 - 23

Published: Jan. 5, 2017

Language: Английский

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Single-cell RNA sequencing reveals intrinsic and extrinsic regulatory heterogeneity in yeast responding to stress

PLoS Biology, Journal Year: 2017, Volume and Issue: 15(12), P. e2004050 - e2004050

Published: Dec. 14, 2017

From bacteria to humans, individual cells within isogenic populations can show significant variation in stress tolerance, but the nature of this heterogeneity is not clear. To investigate this, we used single-cell RNA sequencing quantify transcript single Saccharomyces cerevisiae treated with and without salt explore population identify cellular covariates that influence stress-responsive transcriptome. Leveraging extensive knowledge yeast transcriptional regulation, uncovered regulatory cells, both before after stress. We also discovered a subset appears decouple expression ribosomal protein genes from environmental response manner partly correlated cell cycle unrelated ultradian metabolic cycle. Live-cell imaging expressing pairs fluorescent regulators, including transcription factor Msn2 Dot6, Sfp1, or MAP kinase Hog1, revealed coordinated decoupled nucleocytoplasmic shuttling. Together transcriptomic analysis, our results suggest maintain filter against bursts activation mount upon even unstressed cells.

Language: Английский

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Autonomous Metabolic Oscillations Robustly Gate the Early and Late Cell Cycle

Molecular Cell, Journal Year: 2016, Volume and Issue: 65(2), P. 285 - 295

Published: Dec. 15, 2016

Language: Английский

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Regulation with cell size ensures mitochondrial DNA homeostasis during cell growth

Nature Structural & Molecular Biology, Journal Year: 2023, Volume and Issue: 30(10), P. 1549 - 1560

Published: Sept. 7, 2023

To maintain stable DNA concentrations, proliferating cells need to coordinate replication with cell growth. For nuclear DNA, eukaryotic achieve this by coupling cell-cycle progression, ensuring that is doubled exactly once per cycle. By contrast, mitochondrial typically not strictly coupled the cycle, leaving open question of how correct amount during Here, we show in budding yeast, copy number increases volume, both asynchronously cycling populations and G1 arrest. Our findings suggest cell-volume-dependent maintenance achieved through nuclear-encoded limiting factors, including polymerase Mip1 packaging factor Abf2, whose proportion volume. directly linking protein synthesis thus growth, constant concentrations can be robustly maintained without a for cell-cycle-dependent regulation.

Language: Английский

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