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Andrew Kaplan, Christian Ottmann, Alyson E Fournier
14-3-3sare a family of ubiquitously expressed adaptor proteins that regulate hundreds of functionally diverse 'client proteins.' In humans, there are seven isoforms with conserved structure and function. 14-3-3s typically bind to client proteins at phosphorylated serine/threonine motifs via a linear binding groove. Binding can have a variety of effects on the stability, activity and/or localization of the client protein. 14-3-3s are generating significant interest as potential drug targets for their involvement in cellular homeostasis and disease...
September 13, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Kerem Teke, Nil Guzel, Ali Kemal Uslubas, Murat Kasap, Hasan Yilmaz, Gurler Akpinar, Demir Kursat Yildiz, Ozdal Dillioglugil
Intravesical Bacillus Calmette-Guerin (BCG) is the best treatment modality for progression of non-muscle invasive bladder cancer. We aimed to monitor changes at the proteome level to identify putative protein biomarkers associated with the response of urothelial precancerous lesions to intravesical BCG treatment. The rats were divided into three groups (n = 10/group): control, non-treated, and BCG-treated groups. The non-treated and BCG-treated groups received N-methyl-N-nitrosourea intravesically. BCG Tice-strain was instilled into bladder in BCG-treated group...
September 15, 2017: Cancer Immunology, Immunotherapy: CII
Ali Naderi
This study investigated the network of genes that are co-expressed with androgen receptor (AR) to discover novel AR targets in breast cancer. Bioinformatics analysis of two datasets from breast cancer cell lines resulted in the identification of an AR-gene signature constituted of 98 genes that highly correlated with AR expression. Notably, C1orf64 showed the highest positive correlation with AR across the datasets with a correlation coefficient (CC) of 0.737. In addition, C1orf64 closely correlated with AR expression in primary and metastatic breast tumors and C1orf64 expression was relatively higher in breast tumors with a lower grade and lobular histology...
August 22, 2017: Oncotarget
Janneke H M Teunissen, Marjolein E Crooijmans, Pepijn P P Teunisse, G Paul H van Heusden
BACKGROUND: Ion homeostasis is an essential property of living organisms. The yeast Saccharomyces cerevisiae is an ideal model organism to investigate ion homeostasis at all levels. In this yeast genes involved in high-affinity phosphate uptake (PHO genes) are strongly induced during both phosphate and potassium starvation, indicating a link between phosphate and potassium homeostasis. However, the signal transduction processes involved are not completely understood. As 14-3-3 proteins are key regulators of signal transduction processes, we investigated the effect of deletion of the 14-3-3 genes BMH1 or BMH2 on gene expression during potassium starvation and focused especially on the expression of genes involved in phosphate uptake...
September 6, 2017: BMC Genomics
Hai Lin, Xuelong Jiao, Benxia Yu, Jiangdong Du, HaiYan Xu, Aiping Dong, Chunsheng Wan
OBJECTIVE: The 14-3-3 family of conserved regulatory proteins comprises the isoforms beta (β), gamma (γ), zeta (ζ), sigma (ε), tau (η), and delta (σ), which are overexpressed and associated with a high risk of metastasis and poor survival in hepatocellular carcinoma (HCC). In the present study, we investigated whether serum 14-3-3 isoforms are related to HCC progression and patient survival. METHODS: Serum samples from 63 HCC patients who underwent surgical reSection 104 HCC patients who received non-surgical anti-HCC treatments, 50 patients with liver cirrhosis alone, 45 patients with chronic hepatitis alone, and 50 healthy subjects were collected between January 2006 and December 2010...
August 23, 2017: Cancer Biomarkers: Section A of Disease Markers
Amir Mendelson, Noa Rabinowicz, Yonit Reis, Gil Amarilyo, Liora Harel, Philip J Hashkes, Yosef Uziel
BACKGROUND: This study examined whether the comic book Neta and the Medikidz Explain JIA would improve disease-related knowledge and treatment adherence among patients with juvenile idiopathic arthritis (JIA). METHODS: In this prospective cohort study, JIA patients answered 20 multiple-choice knowledge questions about their disease, before and after reading the comic book. Demographic, clinical, health-related quality of life and adherence data were recorded and correlated to the responses...
September 2, 2017: Pediatric Rheumatology Online Journal
Dominika Chalupska, Andrea Eisenreichova, Bartosz Różycki, Lenka Rezabkova, Jana Humpolickova, Martin Klima, Evzen Boura
Phosphatidylinositol 4-kinase IIIβ (PI4KB) is responsible for the synthesis of the Golgi and trans-Golgi network (TGN) pool of phosphatidylinositol 4-phospahte (PI4P). PI4P is the defining lipid hallmark of Golgi and TGN and also serves as a signaling lipid and as a precursor for higher phosphoinositides. In addition, PI4KB is hijacked by many single stranded plus RNA (+RNA) viruses to generate PI4P-rich membranes that serve as viral replication organelles. Given the importance of this enzyme in cells, it has to be regulated...
August 29, 2017: Journal of Structural Biology
Katsuya Satoh, Ryuichiro Atarashi, Noriyuki Nishida
Sporadic human prion diseases are defined on the basis of clinical features, with periodic sharp discharge (PSD) on electroencephalograms (EEG), a positive 14-3-3 protein assay of CSF samples, and abnormal signals on cerebral cortex on diffusion-weighted (DWI) MR images. It is essential to detect the abnormal prion protein in neuropathological or immunochemical detection of brain tissues when we diagnose definite cases for human prion disease. We performed definite diagnosis of sporadic human prion disease in alive patients...
2017: Methods in Molecular Biology
Sonali Joshi, Jun Yang, Qingfei Wang, Ping Li, Hai Wang, Qingling Zhang, Yan Xiong, Brian F Pickering, Jan Parker-Thornburg, Richard R Behringer, Dihua Yu
The 14-3-3ζ protein belongs to the 14-3-3 family of regulatory eukaryotic proteins that modulate signaling by binding to wide variety of signaling molecules. 14-3-3ζ expression is amplified in over 40% breast cancer patients and is associated with a poor prognosis. Various in vitro and xenograft models have suggested that attenuating 14-3-3ζ expression may provide therapeutic benefits but there has been no study looking at tumor onset and metastasis in breast cancer mouse models with a targeted deletion of 14-3-3ζ...
2017: American Journal of Cancer Research
Robin Beaven, Ricardo Nunes Bastos, Christos Spanos, Pierre Romé, C Fiona Cullen, Juri Rappsilber, Régis Giet, Gohta Goshima, Hiroyuki Ohkura
The meiotic spindle is formed without centrosomes in a large volume of oocytes. Local activation of crucial spindle proteins around chromosomes is important for formation and maintenance of a bipolar spindle in oocytes. We found that phosphodocking 14-3-3 proteins stabilize spindle bipolarity in Drosophila melanogaster oocytes. A critical 14-3-3 target is the minus end-directed motor Ncd (human HSET; kinesin-14), which has well-documented roles in stabilizing a bipolar spindle in oocytes. Phospho docking by 14-3-3 inhibits the microtubule binding activity of the nonmotor Ncd tail...
August 31, 2017: Journal of Cell Biology
Amita Kaundal, Vemanna Ramu, Sunhee Oh, Seonghee Lee, Bikram D Pant, Hee-Kyung Lee, Clemencia Rojas, Muthappa Senthil-Kumar, Kirankumar S Mysore
Plants have complex and adaptive innate immune responses against pathogen infections. Stomata are key entry points for many plant pathogens. Both pathogens and plants regulate stomatal aperture for pathogen entry and defense, respectively. Not all plant proteins involved in stomatal aperture regulation have been identified. Here we report general control non-repressible-4 (GCN4), an AAA+-ATPase family protein, as one of the key proteins regulating stomatal aperture during biotic and abiotic stress. Silencing of GCN4 in Nicotiana benthamiana and Arabidopsis compromises host and nonhost disease resistance due to open stomata during pathogen infection...
August 30, 2017: Plant Cell
Hsing-Chun Kuo, Yur-Ren Kuo, Kam-Fai Lee, Meng-Chiao Hsieh, Cheng-Yi Huang, Yung-Yu Hsieh, Ko-Chao Lee, Hsiang-Lan Kuo, Li-Ya Lee, Wan-Ping Chen, Chin-Chu Chen, Shui-Yi Tung
Background / Aims: Erinacine A, isolated from the ethanol extract of the Hericium erinaceus mycelium, has been demonstrated as a new alternative anticancer medicine. Drawing upon current research, this study presents an investigation of the molecular mechanism of erinacine A inhibition associated with gastric cancer cell growth. METHODS: Cell viability was determined by Annexin V-FITC/propidium iodide staining and migration using a Boyden chamber assay to determine the effects of erinacine A treatment on the proliferation capacity and invasiveness of gastric cancer cells...
August 30, 2017: Cellular Physiology and Biochemistry
Andrew Kaplan, Alyson E Fournier
The goal of developing treatments for central nervous system (CNS) injuries is becoming more attainable with the recent identification of various drugs that can repair damaged axons. These discoveries have stemmed from screening efforts, large expression datasets and an improved understanding of the cellular and molecular biology underlying axon growth. It will be important to continue searching for new compounds that can induce axon repair. Here we describe how a family of adaptor proteins called 14-3-3s can be targeted using small molecule drugs to enhance axon outgrowth and regeneration...
July 2017: Neural Regeneration Research
Cen Li, Soyoung Park, Xiaowen Zhang, Leonard M Eisenberg, Hong Zhao, Zbigniew Darzynkiewicz, Dazhong Xu
Gene 33 (Mig6, ERRFI1) is an adaptor protein with multiple cellular functions. We recently linked Gene 33 to the DNA damage response (DDR) induced by hexavalent chromium [Cr(VI)], but the molecular mechanism remains unknown. Here we show that ectopic expression of Gene 33 triggers DDR in an ATM serine/threonine kinase-dependent fashion and through pathways dependent or not dependent on ABL proto-oncogene 1 non-receptor tyrosine kinase (c-Abl). We observe clear presence of Gene 33 in the nucleus and chromatin fractions of the cell...
August 25, 2017: Journal of Biological Chemistry
Danyal Smani, Sumit Sarkar, James Raymick, Jyotshna Kanungo, Merle G Paule, Qiang Gu
The 14-3-3 proteins are among the most abundant proteins expressed in the brain, comprising about 1% of the total amount of soluble brain proteins. Through phosphoserine- and phosphothreonine-binding motifs, 14-3-3 proteins regulate many signaling proteins and cellular processes including cell death. In the present study, we utilized a well-known kainic acid (KA)-induced excitotoxicity rat model and examined the expression of 14-3-3 and its isoforms in the frontal cortex of KA-treated and control animals. Among the different 14-3-3 isoforms, abundant levels of eta and tau were detected in the frontal cortex, followed by sigma, epsilon, and gamma, while the expression levels of alpha/beta and zeta/delta isoforms were low...
August 24, 2017: Molecular Neurobiology
Xiaoling Li, Yan Wang, Aoxue Zhu, Jie Zhou, Yong Li
Phosphorylation and SUMOylation of the kainate receptor (KAR) subunit GluK2 have been shown to regulate KAR surface expression, trafficking and synaptic plasticity. In addition, our previous study has shown that a phosphorylation-dependent interaction of 14-3-3τ and GluK2a-containing receptors contributes to the slow decay kinetics of native KAR-EPSCs. However, it is unknown whether SUMOylation participates in the regulation of the interaction between 14-3-3τ and GluK2a-containing receptors. Here we report that SUMOylation of PKC, but not GluK2, represses the binding of 14-3-3τ to GluK2a via decreasing the phosphorylation level of GluK2a...
August 24, 2017: Channels
Jayashree Thatte, Lawrence Banks
The Human Papillomavirus (HPV) E6 oncoproteins recruit the cellular ubiquitin ligase, E6AP/UBE3A, to target cellular substrates for proteasome-mediated degradation, and one consequence of this activity is the E6 stimulation of E6AP auto-ubiquitination and degradation. Recent studies identified an autism-linked mutation within E6AP at T485, which was identified as a PKA phospho-acceptor site and which could directly regulate E6AP ubiquitin ligase activity. In this study we have analysed how T485-mediated regulation of E6AP might affect E6 targeting of some of its known substrates...
August 23, 2017: Journal of Virology
Fiona Moghaddas, Rafael Llamas, Dominic De Nardo, Helios Martinez-Banaclocha, Juan J Martinez-Garcia, Pablo Mesa-Del-Castillo, Paul J Baker, Vanessa Gargallo, Anna Mensa-Vilaro, Scott Canna, Ian P Wicks, Pablo Pelegrin, Juan I Arostegui, Seth L Masters
OBJECTIVE: Pyrin-Associated Autoinflammation with Neutrophilic Dermatosis (PAAND) is a recently described monogenic autoinflammatory disease. The causal p.S242R MEFV mutation disrupts a binding motif of the regulatory 14-3-3 proteins within pyrin. Here, we investigate a family with clinical features consistent with PAAND in whom the novel p.E244K MEFV mutation, located in the +2 site of the 14-3-3 binding motif in pyrin, has been found. METHODS: Multiplex cytokine analyses were performed on p...
August 23, 2017: Annals of the Rheumatic Diseases
Dayong Lee, Seul Ki Kim, Kidong Kim, Jung Ryeol Lee, Chang Suk Suh, Seok Hyun Kim
STUDY OBJECTIVE: The study aimed to compare operative outcomes of single-port laparoscopic myomectomy (SP-LM) vs. conventional laparoscopic myomectomy (CLM), including subjective and objective cosmetic aspects. DESIGN: Canadian Task Force Classification I SETTING: University hospital. PATIENTS: Women with uterine myoma scheduled for laparoscopic myomectomy. INTERVENTIONS: Sixty-six women were randomly assigned to either the SP-LM or CLM group...
August 18, 2017: Journal of Minimally Invasive Gynecology
Viet D Dang, Kishore Kumar Jella, Ragy R T Ragheb, Nancy D Denslow, Abdel A Alli
Exosomes are endosome-derived nanovesicles that are involved in cellular communication and signaling. Exosomes are produced by epithelial cells and are found in biologic fluids including blood and urine. The packaged material within exosomes includes proteins and lipids, but the molecular comparison within exosome subtypes is largely unknown. The purpose of this study was to investigate differences between exosomes derived from the apical plasma membrane and basolateral plasma membrane of polarized murine cortical collecting duct principal cells...
August 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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