Cellular quality control by the ubiquitin-proteasome system and autophagy

Science, Journal Year: 2019, Volume and Issue: 366(6467), P. 818 - 822

Published: Nov. 15, 2019

To achieve homeostasis, cells evolved dynamic and self-regulating quality control processes to adapt new environmental conditions prevent prolonged damage. We discuss the importance of two major systems responsible for degradation proteins organelles in eukaryotic cells: ubiquitin-proteasome system (UPS) autophagy. The UPS autophagy form an interconnected network where decision-making is self-organized on basis biophysical parameters (binding affinities, local concentrations, avidity) compartmentalization (through membranes, liquid-liquid phase separation, or formation aggregates). highlight cellular factors that delineate their differential deployment toward macromolecular complexes, phase-separated subcellular structures, membrane-bound organelles. Finally, we emphasize need continuous promotion quantitative mechanistic research into roles human pathophysiology.

Language: Английский

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Circulating tumor cells: biology and clinical significance

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Nov. 22, 2021

Abstract Circulating tumor cells (CTCs) are that have sloughed off the primary and extravasate into circulate in blood. Understanding of metastatic cascade CTCs has tremendous potential for identification targets against cancer metastasis. Detecting these very rare among massive blood is challenging. However, emerging technologies detection profoundly contributed to deepening investigation biology facilitated their clinical application. Current summarized herein, together with advantages disadvantages. The usually dependent on molecular markers, epithelial cell adhesion molecule being most widely used, although markers vary between different types cancer. Properties associated epithelial-to-mesenchymal transition stemness been identified CTCs, indicating increased capacity. Only a small proportion can survive eventually initiate metastases, suggesting an interaction modulation hostile microenvironment essential CTC Single-cell sequencing extensively investigated, enabled researchers reveal genome transcriptome CTCs. Herein, we also review applications especially monitoring response treatment evaluating prognosis. Hence, will continue contribute providing significant insights processes open new avenues useful applications.

Language: Английский

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Post-translational modifications in proteins: resources, tools and prediction methods

Database, Journal Year: 2021, Volume and Issue: 2021

Published: Jan. 1, 2021

Posttranslational modifications (PTMs) refer to amino acid side chain modification in some proteins after their biosynthesis. There are more than 400 different types of PTMs affecting many aspects protein functions. Such happen as crucial molecular regulatory mechanisms regulate diverse cellular processes. These processes have a significant impact on the structure and function proteins. Disruption can lead dysfunction vital biological hence various diseases. High-throughput experimental methods for discovery very laborious time-consuming. Therefore, there is an urgent need computational powerful tools predict PTMs. vast amounts data, which publicly accessible through online databases. In this survey, we comprehensively reviewed major databases related tools. The current challenges were detail well.

Language: Английский

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Structural insights into the catalysis and regulation of E3 ubiquitin ligases

Nature Reviews Molecular Cell Biology, Journal Year: 2016, Volume and Issue: 17(10), P. 626 - 642

Published: Aug. 3, 2016

Language: Английский

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Advancing targeted protein degradation for cancer therapy

Nature reviews. Cancer, Journal Year: 2021, Volume and Issue: 21(10), P. 638 - 654

Published: June 15, 2021

Language: Английский

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Ubiquitin ligases in oncogenic transformation and cancer therapy

Nature reviews. Cancer, Journal Year: 2017, Volume and Issue: 18(2), P. 69 - 88

Published: Dec. 15, 2017

Language: Английский

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Drugging the undruggables: exploring the ubiquitin system for drug development

Cell Research, Journal Year: 2016, Volume and Issue: 26(4), P. 484 - 498

Published: March 22, 2016

Dynamic modulation of protein levels is tightly controlled in response to physiological cues. In mammalian cells, much the degradation carried out by ubiquitin-proteasome system (UPS). Similar kinases, components ubiquitin are often dysregulated, leading a variety diseases, including cancer and neurodegeneration, making them attractive drug targets. However, so far there only handful drugs targeting that have been approved FDA. Here, we review possible therapeutic intervention nodes system, analyze challenges, highlight most promising strategies target UPS.

Language: Английский

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Elusive roles for reactive astrocytes in neurodegenerative diseases

Frontiers in Cellular Neuroscience, Journal Year: 2015, Volume and Issue: 9

Published: Aug. 3, 2015

Astrocytes play crucial roles in the brain and are involved neuroinflammatory response. They become reactive response to virtually all pathological situations such as axotomy, ischemia, infection, neurodegenerative diseases (ND). Astrocyte reactivity was originally characterized by morphological changes (hypertrophy, remodeling of processes) overexpression intermediate filament glial fibrillary acidic protein (GFAP). However, it is unclear how normal supportive functions astrocytes altered their state. In ND, which neuronal dysfunction astrocyte take place over several years or decades, issue even more complex highly debated, with conflicting reports published recently. this review, we discuss studies addressing contribution ND. We describe molecular triggers leading during examine some key may be enhanced disease process, globally affect ND progression. Finally will consider anticipated developments important field. With aim show that detailed study open new perspectives for

Language: Английский

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The Ubiquitin System, Autophagy, and Regulated Protein Degradation

Annual Review of Biochemistry, Journal Year: 2017, Volume and Issue: 86(1), P. 123 - 128

Published: June 20, 2017

This brief disquisition about the early history of studies on regulated protein degradation introduces several detailed reviews ubiquitin system and autophagy.

Language: Английский

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The role of ubiquitination and deubiquitination in cancer metabolism

Molecular Cancer, Journal Year: 2020, Volume and Issue: 19(1)

Published: Oct. 1, 2020

Abstract Metabolic reprogramming, including enhanced biosynthesis of macromolecules, altered energy metabolism, and maintenance redox homeostasis, is considered a hallmark cancer, sustaining cancer cell growth. Multiple signaling pathways, transcription factors metabolic enzymes participate in the modulation metabolism thus, reprogramming highly complex process. Recent studies have observed that ubiquitination deubiquitination are involved regulation cells. As one most important type post-translational modifications, multistep enzymatic process, diverse cellular biological activities. Dysregulation contributes to various disease, cancer. Here, we discuss role which aimed at highlighting importance this modification supporting development new therapeutic approaches for treatment.

Language: Английский

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