Reversible Myc hypomorphism identifies a key Myc-dependency in early cancer evolution.

Germ-line hypomorphism of the pleiotropic transcription factor Myc in mice, either through Myc gene haploinsufficiency or deletion of Myc enhancers, delays onset of various cancers while mice remain viable and exhibit only relatively mild pathologies. Using a genetically engineered mouse model in which Myc expression may be systemically and reversibly hypomorphed at will, we asked whether this resistance to tumour progression is also emplaced when Myc hypomorphism is acutely imposed in adult mice. Indeed, adult Myc hypomorphism profoundly blocked KRas-driven lung and pancreatic cancers, arresting their evolution at the early transition from indolent pre-tumour to invasive cancer.

DoMY-Seq: A yeast two-hybrid-based technique for precision mapping of protein-protein interaction motifs.

Interactions between proteins are fundamental for every biological process and especially important in cell signaling pathways. Biochemical techniques that evaluate these protein-protein interactions (PPIs), such as in vitro pull downs and coimmunoprecipitations, have become popular in most laboratories and are essential to identify and validate novel protein binding partners. Most PPIs occur through small domains or motifs, which are challenging and laborious to map by using standard biochemical approaches because they generally require the cloning of several truncation mutants.

QTY code enables design of detergent-free chemokine receptors that retain ligand-binding activities.

Structure and function studies of membrane proteins, particularly G protein-coupled receptors and multipass transmembrane proteins, require detergents. We have devised a simple tool, the QTY code (glutamine, threonine, and tyrosine), for designing hydrophobic domains to become water soluble without detergents. Here we report using the QTY code to systematically replace the hydrophobic amino acids leucine, valine, isoleucine, and phenylalanine in the seven transmembrane α-helices of CCR5, CXCR4, CCR10, and CXCR7.

Light out-coupling efficiency enhancement in organic light-emitting diodes using a multilayer stacked electrode with sol-gel processed TaO.

We demonstrate enhanced light out-coupling efficiency of organic light-emitting diodes by applying a multilayer stacked electrode structure consisting of fast and cost-effective sol-gel processed tantalum pentoxide (TaO), thin layer of Au and molybdenum trioxide (MoO). The application of the TaO/Au/MoO electrode can modulate the optical characteristics of the device due to the optical microcavity effect. The refractive index of the sol-gel processed TaO thin film varied depending on the annealing temperature and reached a maximum at 400 °C (n = 2.

A dual-scale metal nanowire network transparent conductor for highly efficient and flexible organic light emitting diodes.

Although solution processed metal nanowire (NW) percolation networks are a strong candidate to replace commercial indium tin oxide, their performance is limited in thin film device applications due to reduced effective electrical areas arising from the dimple structure and percolative voids that single size metal NW percolation networks inevitably possess. Here, we present a transparent electrode based on a dual-scale silver nanowire (AgNW) percolation network embedded in a flexible substrate to demonstrate a significant enhancement in the effective electrical area by filling the large percolative voids present in a long/thick AgNW network with short/thin AgNWs. As a proof of concept, the performance enhancement of a flexible phosphorescent OLED is demonstrated with the dual-scale AgNW percolation network compared to the previous mono-scale AgNWs.

Improvement in the Photocurrent of Inverted Organic Solar Cells Using MoO(x)-Doped TAPC as a P-Type Optical Spacer.

In this work, we demonstrate enhancement in the short-circuit current of inverted organic photovoltaic cells (OPVs) using a p-type optical spacer. The p-type optical spacer, which consists of molybdenum oxide (MoO(x))-doped 1,1-bis[(di-4-tolylamino)phenyl]cyclohexane (TAPC), shows improved transmittance at visible light with high electrical conductivity. The electrical field distribution of incident light at the active layer of OPVs can be controlled by tuning the thickness of the optical spacer in the OPVs.

Elevated expression of UBE2T exhibits oncogenic properties in human prostate cancer.

Increased expression of ubiquitin-conjugating enzyme E2T (UBE2T) is reported in human prostate cancer. However, whether UBE2T plays any functional role in prostate cancer development remains unknown. We here report the first functional characterization of UBE2T in prostate carcinogenesis.

Light outcoupling enhancement from top-emitting organic light-emitting diodes made on a nano-sized stochastic texture surface.

An effective method for enhancing the light outcoupling efficiency from top-emitting organic light-emitting diodes (TEOLEDs) with a nano-sized stochastic texture surface (NSTS) is suggested. The broadly distributed pitch and the randomly sized of islands in the NSTS enable the photons that are otherwise trapped to be emitted over the broad emission wavelength range. The NSTS-embedded TEOLEDs have wide angular-dependent emission characteristics and an enhanced external quantum efficiency (EQE).

CUL4A induces epithelial-mesenchymal transition and promotes cancer metastasis by regulating ZEB1 expression.

The ubiquitin ligase CUL4A has been implicated in tumorigenesis, but its contributions to progression and metastasis have not been evaluated. Here, we show that CUL4A is elevated in breast cancer as well as in ovarian, gastric, and colorectal tumors in which its expression level correlates positively with distant metastasis. CUL4A overexpression in normal or malignant human mammary epithelial cells increased their neoplastic properties in vitro and in vivo, markedly increasing epithelial-mesenchymal transition (EMT) and the metastatic capacity of malignant cells.

The role of thioredoxin-1 in suppression of endoplasmic reticulum stress in Parkinson disease.

Endoplasmic reticulum (ER) stress has been implicated in Parkinson disease. We previously reported that thioredoxin 1 (Trx-1) suppressed the ER stress caused by 1-methy-4-phenyl-1,2,3,6-tetrahydropyridine; however, its molecular mechanism remains largely unknown. In the present study, we showed that 1-methyl-4-phenylpyridinium ion (MPP(+)) induced ER stress by activating glucose-regulated protein 78 (GRP78), inositol-requiring enzyme 1α (IRE1α), tumor necrosis factor receptor-associated factor 2 (TRAF2), c-Jun N-terminal kinase (JNK), caspase-12, and C/EBP homologous protein (CHOP) in PC12 cells.

Multiple novel alternative splicing forms of FBXW7α have a translational modulatory function and show specific alteration in human cancer.

FBXW7 acts as a tumor suppressor through ubiquitination and degradation of multiple oncoproteins. Loss of FBXW7 expression, which could be partially attributed by the genomic deletion or mutation of FBXW7 locus, is frequently observed in various human cancers. However, the mechanisms regulating FBXW7 expression still remain poorly understood.

Gremlin is overexpressed in lung adenocarcinoma and increases cell growth and proliferation in normal lung cells.

Background: Gremlin, a member of the Dan family of BMP antagonists, is a glycosylated extracellular protein. Previously Gremlin has been shown to play a role in dorsal-ventral patterning, in tissue remodeling, and recently in angiogenesis. Evidence has previously been presented showing both over- and under-expression of Gremlin in different tumor tissues.

A somatic TSHR mutation in a patient with lung adenocarcinoma with bronchioloalveolar carcinoma, coronary artery disease and severe chronic obstructive pulmonary disease.

In a screen for thoracic malignancy-associated markers, thyroid stimulating hormone receptor (TSHR) was identified as a candidate as it binds to the previously-characterized lung cancer marker NKX2-1. We screened for mutations in all coding regions of the TSHR gene in 96 lung adenocarcinoma samples and their matched adjacent normal lung samples. We found one patient with a somatic mutation at codon 458 (exon 10), which is located at the transmembrane domain where most TSHR mutations have been found in thyroid-related diseases.

Pten regulates Aurora-A and cooperates with Fbxw7 in modulating radiation-induced tumor development.

The Aurora-A kinase gene is frequently amplified and/or overexpressed in a variety of human cancers, leading to major efforts to develop therapeutic agents targeting this pathway. Here, we show that Aurora-A is targeted for ubiquitination and subsequent degradation by the F-box protein FBXW7 in a process that is regulated by GSK3β. Using a series of truncated Aurora-A proteins and site-directed mutagenesis, we identified distinct FBXW7 and GSK3β-binding sites in Aurora-A.

Development of a rapid and practical mutation screening assay for human lung adenocarcinoma.

Mortality after initial diagnosis of lung cancer is higher than from any other cancer. Although mutations in several genes, such as EGFR and K-ras, have been associated with clinical outcome, technical complexity, cost and time have rendered routine screening prohibitive for most lung cancer patients prior to treatment. In this study, using both novel and established technologies, we developed a clinically practical assay to survey the status of three frequently mutated genes in lung cancer (EGFR, K-ras and TP53) and two genes (BRAF and β-catenin) with known hotspot mutations in many other cancers.

Thioredoxin regulates cell cycle via the ERK1/2-cyclin D1 pathway.

Thioredoxin (TRX) is a key component of redox regulation and has been indicated to play an essential role in cell survival and growth. Here, we investigated the molecular mechanism of TRX in the regulation of cell survival and growth by using RNA interference (RNAi) in A549 lung cancer and MCF7 breast cancer cells. TRX knockdown did not significantly increase the basal level of cell death without exposure to stress, but CDDP-induced cell death was enhanced.

Thioredoxin-1 attenuates indomethacin-induced gastric mucosal injury in mice.

Indomethacin is one of non-steroidal anti-inflammatory drugs that are commonly used clinically and often cause gastric mucosal injury as a side effect. Generation of reactive oxygen species (ROS) and activation of apoptotic signaling are involved in the pathogenesis of indomethacin-induced gastric mucosal injury. Thioredoxin-1 (Trx-1) is a small redox-active protein with anti-oxidative activity and redox-regulating functions.

Lipid raft-mediated uptake of cysteine-modified thioredoxin-1: apoptosis enhancement by inhibiting the endogenous thioredoxin-1.

Thioredoxin-1 (TRX) plays important roles in cellular signaling by controlling the redox state of cysteine residues in target proteins. TRX is released in response to oxidative stress and shows various biologic functions from the extracellular environment. However, the mechanism by which extracellular TRX transduces the signal into the cells remains unclear.

Does thioredoxin-1 prevent mitochondria- and endoplasmic reticulum-mediated neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine?

We show that 1-methyl-4-phenylpyridinium ion (MPP(+)), an active metabolite of 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP), induces cytotoxicity via endoplasmic reticulum (ER)- and mitochondria-mediated pathways, and thioredoxin-1 (TRX-1), a redox-active protein, prevents MPTP-induced neurotoxicity. TRX-1 overexpression suppressed reactive oxygen species and the ATP decline caused by MPP(+) in HepG2 cells. MPP(+) activated caspase-12 in PC12 cells and induced cytotoxicity in HeLa-rho(0) cells lacking mitochondrial DNA, as well as in the parental HeLa-S3 cells.

Cytoprotective effects of geranylgeranylacetone against retinal photooxidative damage.

Exposure to excessive light induces retinal photoreceptor cell damage, leading to development and progression of various retinal diseases. We tested the effect of geranylgeranylacetone (GGA), an acyclic polyisoprenoid, on light-induced retinal damage in mice. Oral treatment with GGA (1.

Overexpression of thioredoxin prevents thioacetamide-induced hepatic fibrosis in mice.

Background/aims: Thioredoxin is a small redox-active protein with anti-oxidant and anti-apoptotic effects. We have previously reported that thioacetamide-induced acute hepatitis was attenuated in thioredoxin transgenic mice. The aim of the present study was to investigate the protective effect of thioredoxin for hepatic fibrosis.

Proteasome-dependent degradation of cyclin D1 in 1-methyl-4-phenylpyridinium ion (MPP+)-induced cell cycle arrest.

1-Methyl-4-phenylpyridinium ion (MPP(+)), an active metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, induces cell death and inhibition of cell proliferation in various cells. However, the mechanism whereby MPP(+) inhibits cell proliferation is still unclear. In this study, we found that MPP(+) suppressed the proliferation with accumulation in G(1) phase without inducing cell death in p53-deficient MG63 osteosarcoma cells.

Cysteine-dependent immune regulation by TRX and MIF/GIF family proteins.

Thioredoxin (TRX) superfamily proteins that contain a conserved redox-active site -Cys-Xa.a.-Xa.

Enhanced oxidative stress and impaired thioredoxin expression in spontaneously hypertensive rats.

As oxidative stress plays a crucial role in the development and pathogenesis of hypertension, we analyzed the redox (reduction/oxidation) status in tissues from Wistar-Kyoto rats (WKY), spontaneously hypertensive rats (SHR), and stroke-prone SHR (SHRSP). Expressions of 8-hydroxy-2'-deoxyguanosine, a marker for oxidative stress-induced DNA damage, and protein carbonylation, a marker for oxidation status of proteins, were enhanced in aorta, heart, and kidney from SHR and SHRSP compared with WKY. The expression of redox regulating protein, thioredoxin (TRX), estimated by immunohistochemistry and western blot, and expression of TRX gene estimated by real-time RT-PCR were markedly suppressed in those tissues from SHR and SHRSP compared with WKY.