Arsenic, an ancient drug used in traditional Chinese medicine, has attracted worldwide interest because it shows substantial anticancer activity in patients with acute promyelocytic leukemia (APL). Arsenic trioxide (As2O3) exerts its therapeutic effect by promoting degradation of an oncogenic protein that drives the growth of APL cells, PML-RARalpha (a fusion protein containing sequences from the PML zinc finger protein and retinoic acid receptor alpha). PML and PML-RARalpha degradation is triggered by their SUMOylation, but the mechanism by which As2O3 induces this posttranslational modification is unclear. Here we show that arsenic binds directly to cysteine residues in zinc fingers located within the RBCC domain of PML-RARalpha and PML. Arsenic binding induces PML oligomerization, which increases its interaction with the small ubiquitin-like protein modifier (SUMO)-conjugating enzyme UBC9, resulting in enhanced SUMOylation and degradation. The identification of PML as a direct target of As2O3 provides new insights into the drug's mechanism of action and its specificity for APL.

Abscisic acid (ABA) is an essential hormone for plants to survive environmental stresses. At the center of the ABA signaling network is a subfamily of type 2C protein phosphatases (PP2Cs), which form exclusive interactions with ABA receptors and subfamily 2 Snfl-related kinase (SnRK2s). Here, we report a SnRK2-PP2C complex structure, which reveals marked similarity in PP2C recognition by SnRK2 and ABA receptors. In the complex, the kinase activation loop docks into the active site of PP2C, while the conserved ABA-sensing tryptophan of PP2C inserts into the kinase catalytic cleft, thus mimicking receptor-PP2C interactions. These structural results provide a simple mechanism that directly couples ABA binding to SnRK2 kinase activation and highlight a new paradigm of kinase-phosphatase regulation through mutual packing of their catalytic sites.

The primary nucleation induction time of butyl paraben in pure solvents: acetone, ethyl acetate, methanol, ethanol, and propanol and in 70% and 90% ethanol aqueous mixtures has been determined. At each condition, about 100 experiments have been performed in 5 mL scale to capture the statistics of the nucleation process. The induction times at each condition show a wide variation. The data has been evaluated within the framework of the classical nucleation theory using several of the current approaches. Overall, the data obtained from the different methods of evaluation are surprisingly consistent. At comparable driving forces, nucleation is clearly fastest in acetone and slowest in propanol, with methanol, ethyl acetate, and ethanol in between. Adding water to the ethanol leads to a clear reduction in the nucleation rate. The solid−solution interfacial energy of butyl paraben in the different solvents decreases in the order: 70% ethanol > 90% ethanol > propanol > ethanol > ethyl acetate > methanol > acetone, which is surprisingly well-correlated to a decreasing solvent boiling point. It is shown that the same trend can be found for other systems in the literature. With the assumption that the stronger the bonding in the bulk phases, the higher the interfacial energy becomes, this observation is paralleled by the fact that a metastable polymorph has a lower interfacial energy than the stable form and that a solid compound with a higher melting point appears to have a higher solid-melt and solid-solution interfacial energy.