FEBS Journal

HIV-1 integrase (IN) is essential for integration of the viral cDNA into the host genome. Inhibiting IN is a target for developing anti-HIV therapies. This review focuses on peptide inhibitors of IN, which inhibit the IN interactions and activity. Studies of these peptides increase the understanding of how IN acts and serve as basis for developing new anti-HIV drug leads

Using a small subset of experimental data, an existing detailed kinetic model for steady state behavior of yeast glycolysis was adapted to simulate dynamic behavior. Only small adaptations needed to be made to the original model for a realistic simulation of experimental data for limit cycle oscillations. Largest changes were needed to parameter values for the phosphofructokinase reaction

We validate our model for limit cycle oscillations in yeast glycolysis by simulating a wide range of experiments and it is found to be compliant with the vast majority of data. To our knowledge this is the first time that such a model has been tested against such a wide variety of independent data sets not used for model construction

Previously, sustained oscillations have only been observed at the population level. Using optical tweezers to position yeast cells in a microfluidic chamber, where the cell environment was spatially and temporally controlled, sustained oscillations in individual, isolated cells were observed. The heterogeneous response of the cells was simulated using a detailed kinetic model, assuming small differences in a single internal parameter

EDAG is a hematopoietic transcription regulator involved in hematopoietic proliferation, differentiation and cell apoptosis. EDAG interacted with NPM1 and enhanced NPM1 protein stability. Knockdown of EDAG increased sensitivity of cells to apoptosis induced by imatinib and re-expression of NPM1 attenuated the increased apoptosis, suggesting that the association between EDAG and NPM1 may have pronounced implication in leukemia therapy

Muscle creatine kinase (MCK; EC 2.7.3.2), a 2 × 43 kDa homodimer belonging to the family of guanidino kinases, has a quaternary structure that does not translate into obvious structural or functional advantages over the homologous monomeric arginine kinase. It was still unclear whether MCK subunits functions independently or not. NMR chemical shift perturbation and relaxation experiments indicate that each subunit can bind substrates independently

We studied the possible mechanism of cell cycle arrest by the black tea polyphenols, theaflavins (TF) and thearubigins (TR) in human leukemic U937 and K562 cells. TF and TR treatment augmented expression of p19, p21, p27 and FOXO1but ablated Akt signaling, Hsp90, CDKs, cyclinD1, GSK-3β and β-catenin. These findings suggest a possible anticancer effect of TF and TR through inhibition of cell cycle kinetics

γS-crystallin is a major structural protein of the eye lens. Its deletion in mouse leads to subtle but interesting defects in lens function and lens cell maturation. In particular, organization of actin is altered in the knockout lens. Recombinant γS is able to stabilize F-actin in vitro, suggesting an unexpected chaperone-like role

Butyrylcholinesterase is a potent bioscavenger of organophosphorous neurotoxins. We developed an expression system in insect cells and advantageously used a huprine-based affinity chromatography to purify the recombinant protein. The 2.5-Å crystal structure shows the canonical cholinesterase dimer and the usual unknown ligand bound to the catalytic serine

The SPOT-method was used to identify protein-protein interaction sites in the DFF-complex possibly involved in CAD inhibition. Our data suggest that prevention of CAD homo-dimerisation and local structural perturbation or blocking of the active site constitute a dual inhibitory mechanism to effectively inhibit CAD. Two ICAD-derived peptides were identified that are capable of efficiently inhibiting CAD activity in solution

Based on putative GSK-3β phosphorylation sites within the Slug/Snail2, we explored the significance of GSK-3β-mediated phosphorylation in Slug/Snail2 expression during EMT. Mutation of the putative GSK-3β phosphorylation sites (S92/96A or S100/104A) enhanced the Slug/Snail2-mediated EMT properties of E-cadherin repression and vimentin induction, compared to wild-type Slug/Snail2. S92/96A mutation inhibited degradation of Slug/Snail2 and S100/104A mutation extended nuclear stabilization

An 8 membered water chain in drosophilid ADHs has been investigated. SlADH^T114V has a 3D-structure similar to SlADH^wt but with a broken water chain. The SlADH^T114V mutant follows the same reaction mechanism as the SlADH^wt. Several kinetic parameters differ between SlADH^T114V and SlADH^wt. The water chain acts as a catalytic proton relay and is essential for optimal enzyme activity

P2Y₂ mRNA expression is increased in IBD suffering patients. We have previously showed that the transcription factor NF-κB p65 regulates P2Y₂ transcription in intestinal epithelial cells. In this study, we demonstrated that the transcription factor C/EBPβ also regulates P2Y₂ expression in vitro and in vivo in a mouse model of chemical colitis

In differentiated Caco-2 cells, NF-κB is inhibited via the abrogation of PKCα and PKCθ signaling, leading to a loss of VCAM-1 mRNA expression. C/EBPβ is activated in the differentiated cells leading to increased mRNA expression of ICAM-1. Both VCAM-1 and ICAM-1 proteins are degraded in the proteasome and lysosome in the differentiated cells causing less adhesion to endothelial cells

We reported a dramatic decrease of phosphorylated HSP27 (p-HSP27) in cybrids that harbor the A8344G mutation of mitochondrial DNA in myoclonus epilepsy with ragged-red fibers (MERRF) syndrome. We also showed that p-HSP27 provides significant protection when cells are exposed to different stresses and that nuclear translocation of p-HSP27 correlates with the viability of cells exposed to these stresses