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Open AccessJournal ArticleDOI

Liquid-liquid phase separation in human health and diseases.

TLDR
A review of liquid-liquid phase separation (LLPS) in eukaryotic cells can be found in this paper, where the authors describe the current understanding of LLPS and summarize its physiological functions.
Abstract
Emerging evidence suggests that liquid-liquid phase separation (LLPS) represents a vital and ubiquitous phenomenon underlying the formation of membraneless organelles in eukaryotic cells (also known as biomolecular condensates or droplets). Recent studies have revealed evidences that indicate that LLPS plays a vital role in human health and diseases. In this review, we describe our current understanding of LLPS and summarize its physiological functions. We further describe the role of LLPS in the development of human diseases. Additionally, we review the recently developed methods for studying LLPS. Although LLPS research is in its infancy-but is fast-growing-it is clear that LLPS plays an essential role in the development of pathophysiological conditions. This highlights the need for an overview of the recent advances in the field to translate our current knowledge regarding LLPS into therapeutic discoveries.

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Journal ArticleDOI

Liquid–liquid phase separation in tumor biology

TL;DR: In this article , the authors comprehensively summarize the detailed mechanisms of biomolecular condensate formation and biophysical function and review the recent major advances toward elucidating the multiple mechanisms involved in cancer cell pathology driven by aberrant liquid-liquid phase separation (LLPS).
Journal ArticleDOI

ALS-linked KIF5A ΔExon27 mutant causes neuronal toxicity through gain of function

TL;DR: Results suggest gain of function as an underlying disease mechanism in KIF5A-associated ALS and the mutation relieves motor autoinhibition and increases motor self-association, leading to drastically enhanced processivity on microtubules.
Journal ArticleDOI

Targeting key proteins involved in transcriptional regulation for cancer therapy: Current strategies and future prospective

TL;DR: This review will provide a thorough conspectus of the drug development to target key proteins involved in transcriptional regulation and their impact on future oncotherapy.
Posted ContentDOI

Improved Predictions of Phase Behaviour of Intrinsically Disordered Proteins by Tuning the Interaction Range

Giulio Tesei, +1 more
- 13 Jul 2022 - 
TL;DR: CALVADOS 2 is presented, a coarse-grained model of IDPs that accurately predicts conformational properties and propensity to undergo PS for diverse sequences and solution conditions and which accurately predicts chain compaction and PS propensity for sequences of diverse length and charge patterning.
Journal ArticleDOI

Effects of pH alterations on stress- and aging-induced protein phase separation

TL;DR: In this article , the authors summarized stress-, aging-, and cancer-associated pH changes together with the mechanisms by which cells regulate cytosolic pH homeostasis, along with the functional roles of intracellular pH fluctuation in the regulation of liquid-liquid phase separation.
References
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Journal ArticleDOI

Pattern Recognition Receptors and Inflammation

TL;DR: The role of PRRs, their signaling pathways, and how they control inflammatory responses are discussed.
Journal ArticleDOI

Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor.

TL;DR: High-resolution crystal structures of the receptor-binding domain of the spike protein of SARS-CoV-2 and SARS -CoV in complex with ACE2 provide insights into the binding mode of these coronaviruses and highlight essential ACE2-interacting residues.
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Biomolecular condensates: organizers of cellular biochemistry

TL;DR: This work has shown that liquid–liquid phase separation driven by multivalent macromolecular interactions is an important organizing principle for biomolecular condensates and has proposed a physical framework for this organizing principle.
Journal ArticleDOI

Cyclic GMP-AMP Synthase is a Cytosolic DNA Sensor that Activates the Type-I Interferon Pathway

TL;DR: Results indicate that cGAS is a cytosolic DNA sensor that induces interferons by producing the second messenger cGAMP, which belongs to the nucleotidyltransferase family.
Journal ArticleDOI

Master Transcription Factors and Mediator Establish Super-Enhancers at Key Cell Identity Genes

TL;DR: In this article, the ESC master transcription factors form unusual enhancer domains at most genes that control the pluripotent state, called super-enhancers, which consist of clusters of enhancers that are densely occupied by the master regulators and Mediator.