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Showing papers in "Journal of Biological Chemistry in 2017"


Journal ArticleDOI
TL;DR: NHEJ is a single pathway with multiple enzymes at its disposal to repair DSBs, resulting in a diversity of repair outcomes, including many possible junctional outcomes from one DSB.

336 citations


Journal ArticleDOI
TL;DR: Overall, it is demonstrated how extracellular fluxes quantitatively reflect intracellular ATP turnover and cellular bioenergetics.

322 citations


Journal ArticleDOI
TL;DR: The use of S1QELs and S3 QELs, suppressors of mitochondrial O2̇̄/H2O2 generation that do not inhibit oxidative phosphorylation, are reviewed as tools to characterize the contributions of specific sites in situ and in vivo.

305 citations


Journal ArticleDOI
TL;DR: This review discusses the molecular mechanisms by which the Keap1–Nrf2 system senses and regulates the cellular response to environmental stresses and focuses on the multiple stress-sensing mechanisms of Keap 1 and novel regulatory functions of Nrf2.

283 citations


Journal ArticleDOI
TL;DR: Recent developments in the pursuit of constructing a comprehensive model of Fe/S protein assembly in the mitochondrion are reviewed.

271 citations


Journal ArticleDOI
TL;DR: Results show that low-complexity IDRs can modulate LLPS both positively and negatively, depending on the degree of aromaticity and phosphorylation status, and provide plausible mechanisms by which these sequences could alter RNA granule properties on evolutionary and cellular timescales.

256 citations


Journal ArticleDOI
TL;DR: This work focuses on two autophagic pathways, the chaperone-mediated autophagy and the endosomal microautophagy that rely on the cytosolic chaper one hsc70 for substrate targeting.

237 citations


Journal ArticleDOI
TL;DR: The comparative structural analysis outlines phylum-specific CYP51 features that could direct future rational development of more efficient broad-spectrum antifungal drugs, including the activity of VT-1161 against Candida krusei and Candida glabrata, pathogens that are intrinsically resistant to fluconazole.

214 citations


Journal ArticleDOI
TL;DR: The findings suggest that the BBB does not function independently, but as a module within the greater context of a multicellular neurovascular unit (NVU) that includes neurons, astrocytes, pericytes, and microglia as well as the blood vessels themselves.

207 citations


Journal ArticleDOI
TL;DR: The current findings that elucidate the components, timing, and kinetics of the multivalent role of ubiquitin signals in control of amplitude and selectivity of autophagy pathways as well as their impact on the development of human diseases are reviewed.

205 citations



Journal ArticleDOI
TL;DR: Collectively, its functions explain why lipoic acid is required for cell growth, mitochondrial activity, and coordination of fuel metabolism.

Journal ArticleDOI
TL;DR: It is concluded that miR-145 modulates m6A levels by targeting the 3′-UTR of YTHDF2 mRNA in HCC cells.

Journal ArticleDOI
TL;DR: The role of lncRNAs in transcriptional control of inflammatory responses is reviewed to provide novel targets for the development of new therapeutic strategies.

Journal ArticleDOI
TL;DR: In this article, the authors show that myostatin-modified exosomes produced by Ocy454 cells that had been pre-treated with miR-218 could be taken up by osteoblastic MC3T3 cells, resulting in a marked reduction of Runx2, a key regulator of osteocyte differentiation, and in decreased osteoblast differentiation via the down-regulation of Wnt signaling pathway.

Journal ArticleDOI
TL;DR: It is demonstrated that both human and murine antibodies containing the LALA-PG variant have typical pharmacokinetics in rodents and retain thermostability, enabling efficient knobs-into-holes bispecific antibody production and a robust path to generating highly effector-attenuated bispecial antibodies for preclinical studies.

Journal ArticleDOI
TL;DR: JAK1 is a constitutive TGFβRI binding protein and is absolutely required for phosphorylation of STATs in a SMAD-independent manner within minutes of TGF-β stimulation, and the cooperation between the JAK1-STAT3 and SMAD pathways is critical to the roles of T GF-β in liver fibrosis.

Journal ArticleDOI
TL;DR: Recent developments in disease gene discovery, functional characterization, and shared pathogenic parameters influencing disease pathology that offer promising avenues toward the development of effective therapies are reviewed.

Journal ArticleDOI
TL;DR: The biology of the sirtuin family of proteins, the insulin/insulin-like growth factor (IGF) signaling (IIS) pathway, and the mechanistic target of rapamycin (mTOR) are reviewed.

Journal ArticleDOI
TL;DR: Results indicate that forced ubiquitylation by SNIPERs is a useful method to achieve efficient protein knockdown with potential therapeutic activities and could also be applied to study the role of Ubiquitylation in many cellular processes.

Journal ArticleDOI
TL;DR: Current knowledge on the mode of activation and processing that is initiated by IFN-1 is summarized, in perspective of the resulting phenotypes.

Journal ArticleDOI
TL;DR: An overview of the unique chemistry that cyanobacteria have been co-opted to perform is presented and key lessons learned are highlighted.

Journal ArticleDOI
TL;DR: This work demonstrates that flavonoids specifically inhibit quorum sensing via antagonism of the autoinducer-binding receptors, LasR and RhlR, and confirms their potential as anti-infectives that do not function by traditional bacteriocidal or bacteriostatic mechanisms.

Journal ArticleDOI
TL;DR: A novel mechanism in which INT-767 activation of FXR induces Tgr5 gene expression and increases Ca2+ levels and cAMP activity to stimulate GLP-1 secretion and improve hepatic glucose and lipid metabolism in high-fat diet-induced obese mice is uncovered.

Journal ArticleDOI
TL;DR: A crucial role is demonstrated in the epigenetic regulation of the EMT process in lung cancer cells of MEG3 lncRNA in the recruitment of Polycomb repressive complex-2 and its accessory component, JARID2, to chromatin.

Journal ArticleDOI
TL;DR: It is demonstrated that only Aβ(1–42) contains unique structural features that facilitate membrane insertion and channel formation, now aligning ion channel formation with the differential neurotoxic effect of Aβ (1–40) and A β(1-42) in Alzheimer's disease.

Journal ArticleDOI
TL;DR: It is demonstrated that the role of ROS in mitophagy has been underappreciated as a result of the inefficiency of ROS scavengers to control ROS bursts after high-dose treatment with carbonyl cyanide m-chlorophenylhydrazone and cast doubt on the importance of protein quantity of PINK1 in the recruitment of Parkin to mitochondria.

Journal ArticleDOI
TL;DR: The finding that SLC7A11 overexpression enhances cancer cell dependence on glucose and renders cancer cells more sensitive to glucose starvation-induced cell death is reported and supports the notion that both glucose and glutamate have important roles in maintaining cancer cell survival.

Journal ArticleDOI
TL;DR: It is proposed that an ordered histone code can promote progression through the transcription cycle, providing new mechanistic insight indicating that SEC recruitment to certain acetylated histones on a subset of genes stimulates the subsequent release of paused pol II needed for transcription elongation.

Journal ArticleDOI
TL;DR: Molecular modeling using the Escherichia coli ASNS-B structure has revealed that most of the reported ASD substitutions are located near catalytic sites or within highly conserved regions of the protein.