UPF3B modulates endoplasmic reticulum stress through interaction with inositol-requiring enzyme-1α.

The unfolded protein response (UPR) is a conserved and adaptive intracellular pathway that relieves the endoplasmic reticulum (ER) stress by activating ER transmembrane stress sensors. As a consequence of ER stress, the inhibition of nonsense-mediated mRNA decay (NMD) is due to an increase in the phosphorylation of eIF2α, which has the effect of inhibiting translation. However, the role of NMD in maintaining ER homeostasis remains unclear.

Alternative glucose uptake mediated by β-catenin/RSK1 axis under stress stimuli in mammalian cells.

Cells adapt to stress conditions by increasing glucose uptake as cytoprotective strategy. The efficiency of glucose uptake is determined by the translocation of glucose transporters (GLUTs) from cytosolic vesicles to cellular membranes in many tissues and cells. GLUT translocation is tightly controlled by the activation of Tre-2/BUB2/CDC16 1 domain family 4 (TBC1D4) via its phosphorylation.

The Specific Binding and Promotion Effect of Azoles on Human Aldo-Keto Reductase 7A2.

Human AKR 7A2 broadly participates in the metabolism of a number of exogenous and endogenous compounds. Azoles are a class of clinically widely used antifungal drugs, which are usually metabolized by CYP 3A4, CYP2C19, and CYP1A1, etc. in vivo.

T-2 toxin and deoxynivalenol (DON) exert distinct effects on stress granule formation depending on altered activity of SIRT1.

The T-2 toxin and deoxynivalenol (DON), as the most concerned members of trichothecenes, induce cellular stress responses and various toxic effects. Stress granules (SGs) are rapidly formed in response to stress and play an important role in the cellular stress response. However, it is not known whether T-2 toxin and DON induce SG formation.

Cell fate determined by the activation balance between PKR and SPHK1.

Double-stranded RNA (dsRNA)-dependent protein kinase R (PKR) activation via autophosphorylation is the central cellular response to stress that promotes cell death or apoptosis. However, the key factors and mechanisms behind the simultaneous activation of pro-survival signaling pathways remain unknown. We have discovered a novel regulatory mechanism for the maintenance of cellular homeostasis that relies on the phosphorylation interplay between sphingosine kinase 1 (SPHK1) and PKR during exogenous stress.

Inhibition of EZH2 and activation of ERRγ synergistically suppresses gastric cancer by inhibiting FOXM1 signaling pathway.

Background: Gastric cancer (GC) is a leading cause of cancer-related mortality worldwide, because of the low efficacy of current therapeutic strategies. Estrogen-related receptor γ (ERRγ) was previously showed as a suppressor of GC. However, the mechanism and effective therapeutic method based on ERRγ is yet to be developed.

Phe-125 and Phe-226 of pig cytochrome P450 1A2 stabilize the binding of aflatoxin B and 7-ethoxyresorufin through the key CH/π interactions.

Cytochrome P450 1A2 (CYP1A2) plays important roles in the metabolism of many planar and aromatic drugs and also contributes to the bioactivation of aflatoxin B (AFB) in vivo. To date, the structural basis for CYP1A2's preference to the planar substrates remains unclear. Herein, we investigated the structure-activity relationships for pig CYP1A2 catalyzing AFB and 7-ethoxyresorufin (7-ER).

Multiple CH/π Interactions Maintain the Binding of Aflatoxin B₁ in the Active Cavity of Human Cytochrome P450 1A2.

Human cytochrome P450 1A2 (CYP1A2) is one of the key CYPs that activate aflatoxin B₁ (AFB₁), a notorious mycotoxin, into carcinogenic exo-8,9-epoxides (AFBO) in the liver. Although the structure of CYP1A2 is available, the mechanism of CYP1A2-specific binding to AFB₁ has not been fully clarified. In this study, we used calculation biology to predict a model of CYP1A2 with AFB₁, where Thr-124, Phe-125, Phe-226, and Phe-260 possibly participate in the specific binding.