The Hippo signaling pathway plays a crucial role in tissue growth and tumorigenesis. Core components of the Hippo pathway include the MST1/2 and Lats1/2 kinases. Acting downstream from the Hippo pathway are the YAP/TAZ transcription coactivators, which are inhibited through phosphorylation by Lats. However, upstream signals that regulate the Hippo pathway have not been well delineated. Here we report that stimulation of protease-activated receptors (PARs) activates YAP/TAZ by decreasing phosphorylation and increasing nuclear localization. PAR1 acts through G 12/13 and Rho GTPase to inhibit the Lats1/2 kinase. Our observations establish thrombin as a physiological signal for the Hippo pathway and implicate Hippo-YAP as a key downstream signaling branch of PAR activation.

Activated carbon derived from finger citron residue (FAC) was tested as a new type of adsorbents to remove the harmful dyes (anionic dye methyl orange (MO) and cationic dye methylene blue (MB)) from contaminated water. Liquid phase adsorption experiments were conducted and the maximum adsorptive capacity was determined. Various conditions were evaluated, including initial dye concentration, adsorbent dosage, contact time, solution pH, and temperature. The Langmuir and Freundlich adsorption models were used to describe the equilibrium isotherm and isotherm constant calculation. It was found that the adsorption capacity of FAC is much higher than those of the other types of activated carbons. Maximum equilibrium adsorption capacities of 934.58 mg/g and 581.40 mg/g for MO and MB were achieved.Three simplified kinetic models including pseudo-first-order, pseudo-second-order and intra-particle diffusion equations were used to investigate the adsorption process.The pseudo-second-order equation was followed for adsorption of MO and MB on FAC. Temperature-dependent adsorption behaviors of MO and MB show that the adsorption is a spontaneous and endothermic process accompanying an entropy increases (the driving force of the adsorption). This work indicates that FAC could be employed as a low cost alternative to commercially available activated carbon in the removal of dyes from wastewater.

DNMT1 is an important epigenetic regulator that plays a key role in the maintenance of DNA methylation. Here we determined the crystal structure of DNMT1 in complex with USP7 at 2.9 Å resolution. The interaction between the two proteins is primarily mediated by an acidic pocket in USP7 and Lysine residues within DNMT1's KG linker. This intermolecular interaction is required for USP7-mediated stabilization of DNMT1. Acetylation of the KG linker Lysine residues impair DNMT1–USP7 interaction and promote the degradation of DNMT1. Treatment with HDAC inhibitors results in an increase in acetylated DNMT1 and decreased total DNMT1 protein. This negative correlation is observed in differentiated neuronal cells and pancreatic cancer cells. Our studies reveal that USP7-mediated stabilization of DNMT1 is regulated by acetylation and provide a structural basis for the design of inhibitors, targeting the DNMT1–USP7 interaction surface for therapeutic applications.