LATS1 K751 acetylation blocks activation of Hippo signalling and switches LATS1 from a tumor suppressor to an oncoprotein

Science China Life Sciences - Large tumor suppressor 1 (LATS1) is the key kinase controlling activation of Hippo signalling pathway. Post-translational modifications of LATS1 modulate its kinase...     

OsRLCK160 contributes to flavonoid accumulation and UV-B tolerance by regulating OsbZIP48 in rice

Science China Life Sciences - Plants produce specialized metabolites to adapt to the ever-changing environments. Flavonoids are antioxidants essential for growth, development, and breeding with...     

Permeation mechanism of a two-state potassium channel

A two-state hopping model was proposed to study the permeation of ion channel. The Nernst equation in equilibrium and the Michaelis-Menten relation in steady state were derived from the two-state kinetic model. The current-voltage relationship obtained in the symmetrical solutions case was linear when the applied potential was less than 100 mV, which met Ohm’s law. The conductance-concentration relationship exhibited the saturation property. Moreover, the characteristic time reaching the steady state of the KcsA channel was also discussed. Translated from Acta Biophysica Sinica, 2005, 21(4): 289–294 [译自: 生物物理学报]     

Recent advances in TMEM16A: Structure,function, and disease

TMEM16A (also known as anoctamin 1, ANO1) is the molecular basis of the calcium-activated chloride channels, with ten transmembrane segments. Recently, atomic structures of the transmembrane domains of mouse TMEM16A (mTMEM16A) were determined by single-particle electron cryomicroscopy. This gives us a solid ground to discuss the electrophysiological properties and functions of TMEM16A. TMEM16A is reported to be dually regulated by Ca²⁺ and voltage. In addition, the dysfunction of TMEM16A has been found to be involved in many diseases including cystic fibrosis, various cancers, hypertension, and gastrointestinal motility disorders. TMEM16A is overexpressed in many cancers, including gastrointestinal stromal tumors, gastric cancer, head and neck squamous cell carcinoma (HNSCC), colon cancer, pancreatic ductal adenocarcinoma, and esophageal cancer. Furthermore, overexpression of TMEM16A is related to the occurrence, proliferation, and migration of tumor cells. To date, several studies have shown that many natural compounds and synthetic compounds have regulatory effects on TMEM16A. These small molecule compounds might be novel drugs for the treatment of diseases caused by TMEM16A dysfunction in the future. In addition, recent studies have shown that TMEM16A plays different roles in different diseases through different signal transduction pathways. This review discusses the topology, electrophysiological properties, modulators and functions of TMEM16A in mediates nociception, gastrointestinal dysfunction, hypertension, and cancer and focuses on multiple regulatory mechanisms regarding TMEM16A.     

Galectin-3 exacerbates ox-LDL-mediated endothelial injury by inducing inflammation via integrin β1-RhoA-JNK signaling activation

Oxidized low-density lipoprotein (Ox-LDL)-induced endothelial cell injury plays a crucial role in the pathogenesis of atherosclerosis (AS). Plasma galectin-3 (Gal-3) is elevated inside and drives diverse systemic inflammatory disorders, including cardiovascular diseases. However, the exact role of Gal-3 in ox-LDL-mediated endothelial injury remains unclear. This study explores the effects of Gal-3 on ox-LDL-induced endothelial dysfunction and the underlying molecular mechanisms. In this study, Gal-3, integrin β1, and GTP-RhoA in the blood and plaques of AS patients were examined by ELISA and western blot respectively. Their levels were found to be obviously upregulated compared with non-AS control group. CCK8 assay and flow cytometry analysis showed that Gal-3 significantly decreased cell viability and promoted apoptosis in ox-LDL-treated human umbilical vascular endothelial cells (HUVECs). The upregulation of integrinβ1, GTP-RhoA, p-JNK, p-p65, p-IKKα, and p-IKKβ induced by ox-LDL was further enhanced by treatment with Gal-3. Pretreatment with Gal-3 increased expression of inflammatory factors (interleukin [IL]-6, IL-8, and IL-1β), chemokines(CXCL-1 and CCL-2) and adhesion molecules (VCAM-1 and ICAM-1). Furthermore, the promotional effects of Gal-3 on NF-κB activation and inflammatory factors in ox-LDL-treated HUVECs were reversed by the treatments with integrinβ1-siRNA or the JNK inhibitor. We also found that integrinβ1-siRNA decreased the protein expression of GTP-RhoA and p-JNK, while RhoA inhibitor partially reduced the upregulated expression of p-JNK induced by Gal-3. In conclusion, our finding suggests that Gal-3 exacerbates ox-LDL-mediated endothelial injury by inducing inflammation via integrin β1-RhoA-JNK signaling activation.     

ESM-1 promotes adhesion between monocytes and endothelial cells under intermittent hypoxia

Intermittent hypoxia (IH), the key property of obstructive sleep apnea (OSA), is closely associated with endothelial dysfunction. Endothelial-cell-specific molecule-1 (ESM-1, Endocan) is a novel, reported molecule linked to endothelial dysfunction. The aim of this study is to evaluate the effect of IH on ESM-1 expression and the role of ESM-1 in endothelial dysfunction. We found that serum concentration of ESM-1, inter-cellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) is significantly higher in patients with OSA than healthy volunteers (p < 0.01). The expression of ESM-1, hypoxia-inducible factor-1 alpha (HIF-1α), and vascular endothelial growth factor (VEGF) was significantly increased in human umbilical vein endothelial cells (HUVECs) by treated IH in a time-dependent manner. HIF-1α short hairpin RNA and vascular endothelial growth factor receptor (VEGFR) inhibitor inhibited the expression of ESM-1 in HUVECs. ICAM-1 and VCAM-1 expressions were significantly enhanced under IH status, accompanied by increased monocyte–endothelial cell adhesion rate ( p < 0.001). Accordingly, ESM-1 silencing decreased the expression of ICAM-1 and VCAM-1 in HUVECs, whereas ESM-1 treatment significantly enhanced ICAM-1 expression accompanied by increasing adhesion ability. ESM-1 is significantly upregulated by the HIF-1α/VEGF pathway under IH in endothelial cells, playing a critical role in enhancing adhesion between monocytes and endothelial cells, which might be a potential target for IH-induced endothelial dysfunction.     

Rice sulfoquinovosyltransferase SQD2.1 mediates flavonoid glycosylation and enhances tolerance to osmotic stress

Sulfoquinovosyltransferase 2 (SQD2) catalyses the final step in the sulfoquinovosyldiacylglycerol (SQDG) biosynthetic pathway. It is involved in the phosphate starvation response. Here, we show that rice SQD2.1 has dual activities catalysing SQDG synthesis and flavonoid glycosylation. SQD2.1 null mutants (sqd2.1) in rice had decreased levels of glycosidic flavonoids, particularly apigenin 7‐O‐glucoside (A7G), whereas these metabolites were increased in rice plants overexpressing SQD2.1. The sqd2.1 mutants and SQD2.1 overexpressing lines showed reduced and enhanced, respectively, tolerance to salinity and drought. Treating the sqd2.1 mutants with A7G decreased oxidative damage and restored stress tolerance to the wild‐type levels. These findings demonstrate that SQD2.1 has a novel function in the glycosylation of flavonoids that is required for osmotic stress tolerance in rice. The novel activity of SQD2.1 in the production of glycosidic flavonoids improves scavenging of reactive oxygen species and protects against excessive oxidation.