Showing papers in "Journal of Biological Chemistry in 2019"

TL;DR: An overview of the molecular underpinnings of the formation and regulation of these membraneless organelles are provided and new light on neurodegenerative diseases is shone on.

TL;DR: Recent insights into how post-translational modifications of RBPs regulate phase separation and RNP granule dynamics are reviewed, in particular arginine (Arg)-methylation and phosphorylation.

TL;DR: Some of the main methods surrounding cryo-EM with an emphasis specifically on single-particle analysis are reviewed, and challenges, open questions, and opportunities for methodology development are highlighted.

TL;DR: This review will present an overview of the current understanding of O-GlcNAc's regulation, functions, and roles in chronic diseases of aging.

TL;DR: The results reveal that PcG condensates assemble through liquid–liquid phase separation (LLPS) and suggest that phase-separated condensate can organize Pcg-bound chromatin, and reveal a mechanism underlying the assembly of CBX2–PRC1 condensating.

TL;DR: How BiP's functional cycle and interactions with ERdjs enable it to regulate protein homeostasis in the ER and ensure protein quality control is discussed.

TL;DR: It is demonstrated that amyloid formation by the LCD is controlled by electrostatic repulsion, and that the liquid droplet environment strongly accelerates LCD fibrillation and that its aggregation under LLPS conditions involves several distinct events, culminating in rapid assembly of fibrillar aggregates that emanate from within mature liquid droplets.

TL;DR: Although considerable progress has been made in the development and application of new techniques, it is clear that further development is required to fully assess the relative importance of protein oxidation and to determine whether an oxidation is a cause, or merely a consequence, of injurious processes.

TL;DR: The information gained from exploring the mechanism of the bacterial chaperone system will provide the groundwork for understanding the more complex eukaryotic HSp90 system and its modulation by Hsp90 co-chaperones.

TL;DR: The discovery of the insulin-responsive glucose transporter type 4 (GLUT4) protein in 1988 inspired its molecular cloning in the following year and spurred numerous cellular mechanistic studies laying the foundations for how insulin regulates glucose uptake by muscle and fat cells.

TL;DR: Hsp70 chaperones are central hubs of the protein quality control network and collaborate with co-chaperones having a J-domain having a flexible loop and a conserved His–Pro–Asp motif required for ATP hydrolysis by Hsp70s to facilitate many protein-folding processes that (re)establish protein homeostasis.

TL;DR: This review summarizes recent work linking liquid phase separation to neurodegeneration, highlighting a pathological role for altered phase behavior and material properties of proteins assembled via liquidphase separation.

TL;DR: This review will focus on how mechanical perturbations are sensed through changes in the actin cytoskeleton and mechanosensors at focal adhesions, adherens junctions, and the nuclear envelope to regulate YAP/TAZ.

TL;DR: It is argued that prion-like low-complexity regions (LCRs) are key regulators of protein solubility and folding and that prions have evolved to regulate protein phase behavior and to protect proteins against proteotoxic damage.

TL;DR: New roles and new cofactors, as well as variations in structure and regulation of sHsps, have emerged, and current evidence suggests that smaller oligomers are more active chaperones.

TL;DR: The modes of signaling to and levels of regulation of the E. coli general Stress Response are discussed and are used as a basis for comparison with the general stress response in other bacteria with the aim of extracting key principles that are common among different species and highlighting important unanswered questions.

TL;DR: Analysis of the NPC1 and NPC2 structures and biochemical properties, together with new structures of the related Patched protein, provides new clues to the mechanisms by which NPC proteins may function.

TL;DR: It is shown that certain members within the Loop 1, mini-Loop 1, and FMN-binding classes of gut microbial GUS enzymes can reactivate estrogens from their inactive glucuronides, and that a Loop 1 GUS-specific inhibitor is not capable of reducing the development of tumors in the PyMT mouse model of breast cancer.

TL;DR: Key features, such as extraordinary sensitivity, which make the process of phase separation ideally suited to meet a range of sensory challenges cells encounter are discussed.

TL;DR: It is demonstrated that tau LLPS is largely driven by intermolecular electrostatic interactions between the negatively charged N-terminal and positively charged middle/C- terminal regions, whereas hydrophobic interactions play a surprisingly small role.

TL;DR: An assay based on FRET is used that exploits a HEK293T “biosensor” cell line stably expressing α-syn (A53T)-CFP/YFP fusion proteins to detect α- synuclein seeds in brain extracts from PD and MSA patients, consistent with the idea that distinctα-syn strains underlie PD andMSA.

TL;DR: In this article, the authors summarize commonly used methods to investigate various forms of liquid-liquid phase separation occurring both in 3D aqueous solution and on 2D membrane bilayers, such as LLPS condensates arising from intrinsically disordered proteins or structured modular protein domains.

TL;DR: A deeper understanding of how mitochondrial protein quality control mechanisms are coordinated across these distinct biological levels should help explain why these mechanisms fail with age and, ultimately, how routes to intervention might be attained.

TL;DR: A comprehensive analysis of GPCR gene expression, copy number variation, and mutational signatures in 33 cancer types is presented and highlights the emerging role of G PCRs as part of oncocrine networks promoting tumor growth, dissemination, and immune evasion.

TL;DR: It is concluded that it is possible to prevent CRS by using “all-in-one” GMCSF-knockout CAR T-cells and this approach may eliminate the need for anti-CRS treatment and may improve the overall safety ofCAR T-cell therapies for cancer patients.

TL;DR: It is demonstrated that PANX1 deletion protects against renal IRI by regulating ferroptotic cell death and is a potential therapeutic target for the management of acute kidney injury (AKI) during the perioperative period.

TL;DR: The regulatory role of translation elongation in protein biogenesis and what factors influence elongation kinetics are discussed and how changes in translation kinetics signal downstream pathways that dictate the fate of nascent polypeptides are described.

TL;DR: SRC-mediated YAP/TAZ activity promotes tumor growth and enhances metastasis and that SRC-dependent tumor progression depends, at least in part, on YAP and TAZ, suggest that therapies targeting SRC could help manage some YAP-TAZ-dependent cancers.

TL;DR: An overview of the extensive history of protease research is provided, highlighting a few discoveries and roles of proteases in vivo and future directions in this highly diverse and thriving research area are addressed.

TL;DR: Results indicate that TM-induced UPR activates functional autophagy, and whereas IRE1 is a negative regulator, PERK and ATF4 are required at distinct steps in the autophagic pathway.