Cell Signaling and Stress Responses

Cold Spring Harbor Perspectives in Biology, Год журнала: 2016, Номер 8(10), С. a006072 - a006072

Опубликована: Окт. 1, 2016

Stress-signaling pathways are evolutionarily conserved and play an important role in the maintenance of homeostasis. These also critical for adaptation to new cellular environments. The endoplasmic reticulum (ER) unfolded protein response (UPR) is activated by biosynthetic stress leads a compensatory increase ER function. JNK p38 MAPK signaling control adaptive responses intracellular extracellular stresses, including environmental changes such as UV light, heat, hyperosmotic conditions, exposure inflammatory cytokines. Metabolic caused high-fat diet represents example stimulus that coordinately activates both UPR JNK/p38 pathways. Chronic activation these stress-response ultimately causes metabolic associated with obesity altered insulin sensitivity. pathways, therefore, represent potential targets therapeutic intervention other disease processes.

Язык: Английский

---

Systems biology primer: the basic methods and approaches

Essays in Biochemistry, Год журнала: 2018, Номер 62(4), С. 487 - 500

Опубликована: Окт. 4, 2018

Systems biology is an integrative discipline connecting the molecular components within a single biological scale and also among different scales (e.g. cells, tissues organ systems) to physiological functions organismal phenotypes through quantitative reasoning, computational models high-throughput experimental technologies. uses wide range of methodologies decode information flow from genes, proteins other subcellular signaling, regulatory functional pathways control cell, tissue, level functions. The methods used in systems provide systems-level insights understand interactions dynamics at various scales, tissues, organs organisms. In recent years, framework has enabled research pharmacology precision medicine for complex diseases. Here, we present brief overview current biology.

Язык: Английский

---

Dynamic regulation of RAS and RAS signaling

Biochemical Journal, Год журнала: 2023, Номер 480(1), С. 1 - 23

Опубликована: Янв. 6, 2023

RAS proteins regulate most aspects of cellular physiology. They are mutated in 30% human cancers and 4% developmental disorders termed Rasopathies. cycle between active GTP-bound inactive GDP-bound states. When active, they can interact with a wide range effectors that control fundamental biochemical biological processes. Emerging evidence suggests not simple on/off switches but sophisticated information processing devices compute cell fate decisions by integrating external internal cues. A critical component this function is the dynamic regulation activation downstream signaling allows to produce rich nuanced spectrum outputs. We discuss recent findings how dynamics its regulated. Starting from structural properties wild-type mutant their cycle, we examine higher molecular assemblies, effector interactions outputs, all under aspect regulation. also consider computational mathematical modeling approaches contribute analyze understand pleiotropic functions health disease.

Язык: Английский

---

Alternatives of Animal Models for Biomedical Research: a Comprehensive Review of Modern Approaches

Stem Cell Reviews and Reports, Год журнала: 2024, Номер 20(4), С. 881 - 899

Опубликована: Март 1, 2024

Язык: Английский

---

Two-Component Sensing and Regulation: How Do Histidine Kinases Talk with Response Regulators at the Molecular Level?

Annual Review of Microbiology, Год журнала: 2019, Номер 73(1), С. 507 - 528

Опубликована: Июнь 21, 2019

Perceiving environmental and internal information reacting in adaptive ways are essential attributes of living organisms. Two-component systems relevant protein machineries from prokaryotes lower eukaryotes that enable cells to sense process signals. Implicating sensory histidine kinases response regulator proteins, both components take advantage phosphorylation flexibility switch conformations a signal-dependent way. Dozens two-component act simultaneously any given cell, challenging our understanding about the means ensure proper connectivity. This review dives into molecular level, attempting summarize an emerging picture how cognate regulators achieve required efficiency, specificity, directionality signaling pathways, properties rely on protein:protein interactions. α helices carry through long distances, fine combination loose specific kinase/regulator interactions, malleable reaction centers built when two meet emerge as universal principles.

Язык: Английский

---

Signaling Networks: Information Flow, Computation, and Decision Making

Cold Spring Harbor Perspectives in Biology, Год журнала: 2015, Номер 7(4), С. a005934 - a005934

Опубликована: Апрель 1, 2015

Evren U. Azeloglu and Ravi Iyengar Department of Pharmacology Systems Therapeutics Biology Center New York, Mount Sinai School Medicine, York 10029 Correspondence: ravi.iyengar{at}mssm.edu

Язык: Английский

---

Protein Regulation in Signal Transduction

Cold Spring Harbor Perspectives in Biology, Год журнала: 2016, Номер 8(6), С. a005918 - a005918

Опубликована: Июнь 1, 2016

Michael J. Lee and B. Yaffe David H. Koch Institute for Integrative Cancer Research at MIT, Department of Biology Biological Engineering, Massachusetts Technology, Cambridge, 02139 Correspondence: myaffe{at}mit.edu

Язык: Английский

---

Multilayered Control of Protein Turnover by TORC1 and Atg1

Cell Reports, Год журнала: 2019, Номер 28(13), С. 3486 - 3496.e6

Опубликована: Сен. 1, 2019

The target of rapamycin complex 1 (TORC1) is a master regulator cell homeostasis, which promotes anabolic reactions and synchronously inhibits catabolic processes such as autophagy-mediated protein degradation. Its prime autophagy Atg13, subunit the Atg1 kinase that acts gatekeeper canonical autophagy. To study whether activities TORC1 are coupled through additional, more intricate control mechanisms than simply this linear pathway, we analyzed epistatic relationship between by using quantitative phosphoproteomics. Our in vivo data, combined with targeted vitro assays, not only uncover numerous effectors, but also suggest distinct bi-directional regulatory feedback loops characterize Atg29 commonly regulated downstream both Atg1. Thus, an exquisitely multilayered network appears to coordinate robustly tune response nutritional cues.

Язык: Английский

---

Towards the Idea of Molecular Brains

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(21), С. 11868 - 11868

Опубликована: Ноя. 1, 2021

How can single cells without nervous systems perform complex behaviours such as habituation, associative learning and decision making, which are considered the hallmark of animals with a brain? Are there molecular that underlie cognitive properties equivalent to those This review follows development idea brains from Darwin’s “root brain hypothesis”, through bacterial chemotaxis, recent discovery neuron-like r-protein networks in ribosome. By combining structural biology view Bayesian approach, this explores evolutionary labyrinth information processing across scales. Ribosomal protein open window into what were probably earliest signalling emerge before radiation three kingdoms. While ribosomal characterised by long-lasting interactions between their nodes, cell essentially based on transient interactions. As corollary, while signals propagated persistent may be ephemeral, whose constrain diffusing cytoplasm durable time, post-translational modifications proteins or second messenger synthesis. The duration nature signals, turn, implies different mechanisms for integration multiple making. Evolution then reinvented metazoans. simple display architectural functional analogies comparison could suggest scale invariance processing. At level, significant complexification eukaryotic is associated burst acquisition new conserved aromatic amino acids. Knowing residues play critical role allosteric receptors channels, observation suggests general π charged acids signal We think these findings provide basis designing future computers organic processors.

Язык: Английский

---

Mutual repression between JNK/AP-1 and JAK/STAT stratifies senescent and proliferative cell behaviors during tissue regeneration

PLoS Biology, Год журнала: 2023, Номер 21(5), С. e3001665 - e3001665

Опубликована: Май 30, 2023

Epithelial repair relies on the activation of stress signaling pathways to coordinate tissue repair. Their deregulation is implicated in chronic wound and cancer pathologies. Using TNF-α/Eiger-mediated inflammatory damage Drosophila imaginal discs, we investigate how spatial patterns behaviors arise. We find that Eiger expression, which drives JNK/AP-1 signaling, transiently arrests proliferation cells center associated with a senescence program. This includes production mitogenic ligands Upd family, allows JNK/AP-1-signaling act as paracrine organizers regeneration. Surprisingly, cell-autonomously suppress via Ptp61F Socs36E, both negative regulators JAK/STAT signaling. As suppressed at damage, compensatory occurs by periphery. Mathematical modelling suggests cell-autonomous mutual repression between core regulatory network essential spatially separate into bistable domains distinct cellular tasks. Such stratification for proper repair, coactivation same creates conflicting signals cell cycle progression, leading excess apoptosis senescently stalled organize field. Finally, demonstrate separation senescent proliferative not only upon but also Ras V12 , scrib tumors. Revealing this previously uncharacterized JNK/AP-1, JAK/STAT, has important implications our conceptual understanding pathologies, tumor microenvironments.

Язык: Английский

---