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Lina Zhou, Hongzhou Hou, Tao Yang, Yuke Lian, Yan Sun, Zhiyuan Bian, Chongying Wang
Hydrogen peroxide (H2 O2 ) is the key factor in many physiological and metabolic processes in plants. During seed germination, exogenous H2 O2 application influences gravitropism and induces curvature of the primary root in grass pea and pea seedlings. However, it remains unclear whether and how this happens in the model plant Arabidopsis thaliana. In the present study, the effect of exogenous H2 O2 on the gravitropic response of primary roots during Arabidopsis seed germination was studied using histology and molecular biology approaches...
May 15, 2018: Plant Physiology and Biochemistry: PPB
Jill J Bouchard, Junchao Xia, David A Case, Jeffrey W Peng
Many signaling proteins consist of globular domains connected by flexible linkers that allow for substantial domain motion. Because these domains often serve as complementary functional modules, the possibility of functionally important domain motions arises. To explore this possibility, we require knowledge of the ensemble of protein conformations sampled by interdomain motion. Measurements of NMR residual dipolar couplings (RDCs) of backbone NH bonds offer a per-residue characterization of interdomain dynamics, as the couplings are sensitive to domain orientation...
May 15, 2018: Journal of Molecular Biology
Guoliang Fan, Lin Wang, Jia Xu, Ping Jiang, Wei Wang, Ying Huang, Minggang Lv, Shaoting Liu
Increasing evidence indicates that peptidylprolyl cis/trans isomerase, NIMA-interacting 1 (Pin1) plays a decisive role in a variety of cancers. Nevertheless, its function in laryngeal squamous cell carcinoma (LSCC) has not been elaborated. The aim of this study is to determine the role of Pin1 in LSCC. Here, we established stably transfected Hep-2 cells with low expression of Pin1. Intriguingly, ability of cell proliferation, migration and invasion was significantly inhibited in Pin1-silenced Hep-2 cells. Similarly, knockdown of Pin1 induced apoptosis of Hep-2 cells, as evidenced by increased expression of cleaved-caspase-3, cleaved-PARP, and bax, and decreased expression of bcl2...
May 16, 2018: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
Melissa A O'Neal, Nancy R Stallings, James S Malter
Therapeutics to effectively treat Alzheimer's disease (AD) are lacking. In vitro, animal and human studies have implicated the excessive activation of the protein phosphatase calcineurin (CN) as an early step in the pathogenesis of AD. We discuss recent data showing that the prolyl isomerase Pin1 is suppressed by CN-mediated dephosphorylation induced by Aβ42 signaling. Pin1 loss directly leads to the reductions in dendritic spines and synapses characteristic of early AD pathology. Pin1 activity, and synapse and dendritic spine numbers are rescued by FK506, a highly specific and United States Food and Drug Administration approved CN inhibitor...
May 14, 2018: ACS Chemical Neuroscience
Garam Kim, Jin-Young Kim, Sung-Chul Lim, Kwang Youl Lee, Okyun Kim, Hong Seok Choi
Melanoma is among the most aggressive and treatment-resistant human cancers. Aberrant histone H3 methylation at Lys 9 (H3K9) correlates with carcinogenic gene silencing, but the significance of suppressor of variegation 3-9 homolog 1 (SUV39H1), an H3K9-specific methyltransferase, in melanoma initiation and progression remains unclear. Here, we show that SUV39H1-mediated H3K9 trimethylation facilitates retinoblastoma ( RB) 1 promoter CpG island methylation by interacting with DNA methyltransferase 3A and decreasing RB mRNA and protein in melanoma cells...
May 11, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Concetta Russo Spena, Lucia De Stefano, Stefano Palazzolo, Barbara Salis, Carlotta Granchi, Filippo Minutolo, Tiziano Tuccinardi, Roberto Fratamico, Sara Crotti, Sara D'Aronco, Marco Agostini, Giuseppe Corona, Isabella Caligiuri, Vincenzo Canzonieri, Flavio Rizzolio
Pin1, a prolyl isomerase that sustains tumor progression, is overexpressed in different types of malignancies. Functional inactivation of Pin1 restrains tumor growth and leaves normal cells unaffected making it an ideal pharmaceutical target. Although many studies on Pin1 have focused on malignancies that are influenced by sex hormones, studies in ovarian cancer have lagged behind. Here, we show that Pin1 is an important therapeutic target in high-grade serous epithelial ovarian cancer. Knock down of Pin1 in ovarian cancer cell lines induces apoptosis and restrains tumor growth in a syngeneic mouse model...
May 7, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Ke Wu, Juan He, Wenchen Pu, Yong Peng
MicroRNAs (miRNAs) are conserved small non-coding RNAs that play an important role in the regulation of gene expression and participate in a variety of biological processes. The biogenesis of miRNAs is tightly controlled at multiple steps, such as transcription of miRNA genes, processing by Drosha and Dicer, and transportation of precursor miRNAs (pre-miRNAs) from the nucleus to the cytoplasm by exportin-5 (XPO5). Given the critical role of nuclear export of pre-miRNAs in miRNA biogenesis, any alterations of XPO5, resulting from either genetic mutation, epigenetic change, abnormal expression level or posttranslational modification, could affect miRNA expression and thus have profound effects on tumorigenesis...
April 30, 2018: Genomics, Proteomics & Bioinformatics
Arjun Khakhar, Alexander R Leydon, Andrew C Lemmex, Eric Klavins, Jennifer L Nemhauser
Developmental programs sculpt plant morphology to meet environmental challenges, and these same programs have been manipulated to increase agricultural productivity1,2 . Hormones coordinate these programs, creating chemical circuitry3 that has been represented in mathematical models4,5 ; however, model-guided engineering of plant morphology has been limited by a lack of tools6,7 . Here, we introduce a novel set of synthetic and modular <u>h</u>ormone <u>a</u>ctivated <u>C</u>as9-based <u>r</u>epressors (HACRs) in Arabidopsis thaliana that respond to three hormones: auxin, gibberellins and jasmonates...
May 1, 2018: ELife
Eleri Short, Margaret Leighton, Gul Imriz, Dongbin Liu, Naomi Cope-Selby, Flora Hetherington, Andrei Smertenko, Patrick J Hussey, Jennifer F Topping, Keith Lindsey
The epidermis is hypothesized to play a signalling role during plant development. One class of mutants showing defects in signal transduction and radial patterning are those in sterol biosynthesis. The expectation is that living cells require sterols, but it is not clear that all cell types express sterol biosynthesis genes. The HYDRA1 ( HYD1 ) gene of Arabidopsis encodes sterol Δ8-Δ7 isomerase, and although hyd1 seedlings are defective in radial patterning across several tissues, we show that the HYD1 gene is expressed most strongly in the root epidermis...
April 25, 2018: Development
Morris Nechama, Jeahoo Kwon, Shuo Wei, Adrian Tun Kyi, Robert S Welner, Iddo Z Ben-Dov, Mohamed S Arredouani, John M Asara, Chun-Hau Chen, Cheng-Yu Tsai, Kyle F Nelson, Koichi S Kobayashi, Elliot Israel, Xiao Zhen Zhou, Linda K Nicholson, Kun Ping Lu
Interleukin 33 (IL-33) is among the earliest-released cytokines in response to allergens that orchestrate type 2 immunity. The prolyl cis-trans isomerase PIN1 is known to induce cytokines for eosinophil survival and activation by stabilizing cytokines mRNAs, but the function of PIN1 in upstream signaling pathways in asthma is unknown. Here we show that interleukin receptor associated kinase M (IRAK-M) is a PIN1 target critical for IL-33 signaling in allergic asthma. NMR analysis and docking simulations suggest that PIN1 might regulate IRAK-M conformation and function in IL-33 signaling...
April 23, 2018: Nature Communications
Puneet Talwar, Renu Gupta, Suman Kushwaha, Rachna Agarwal, Luciano Saso, Shrikant Kukreti, Ritushree Kukreti
Alzheimer's disease (AD) is genetically complex with multifactorial etiology. Here, we aim to identify the potential viral pathogens leading to aberrant inflammatory and oxidative stress response in AD along with potential drug candidates using systems biology approach. We retrieved protein interactions of amyloid precursor protein (APP) and tau protein (MAPT) from NCBI and genes for oxidative stress from NetAge, for inflammation from NetAge and InnateDB databases. Genes implicated in aging were retrieved from GenAge database and two GEO expression datasets...
April 19, 2018: Current Neuropharmacology
Giuseppe Legname, Tommaso Virgilio, Edoardo Bistaffa, Chiara Maria Giulia De Luca, Marcella Catania, Paola Zago, Elisa Isopi, Ilaria Campagnani, Fabrizio Tagliavini, Giorgio Giaccone, Fabio Moda
Pin1 is a peptidyl-prolyl isomerase that induces the cis-trans conversion of specific Ser/Thr-Pro peptide bonds in phosphorylated proteins, leading to conformational changes through which Pin1 regulates protein stability and activity. Since down-regulation of Pin1 has been described in several neurodegenerative disorders, including Alzheimer's Disease (AD), Parkinson's Disease (PD) and Huntington's Disease (HD), we investigated its potential role in prion diseases. Animals generated on wild-type (Pin1+/+ ), hemizygous (Pin1+/- ) or knock-out (Pin1-/- ) background for Pin1 were experimentally infected with RML prions...
April 20, 2018: Prion
Miao Liu, Haihua Zhang, Xianzhi Fang, Yongsong Zhang, Chongwei Jin
This study examines the association of auxin with ethylene and nitric oxide (NO) in regulating the magnesium-deficiency-induced root hair development in Arabidopsis thaliana. With magnesium (Mg) deficiency, both ethylene and NO promoted the elevation of root auxin levels in roots by inducing the expression of AUX1, PIN1, and PIN2 transporters. In turn, auxin stimulated ethylene and NO production by activating the activities of 1-aminocyclopropane-1-carboxylate (ACC) oxidase (ACO), ACC synthase (ACS), nitrate reductase (NR), and NO synthase-like (NOS-L)...
April 16, 2018: Plant & Cell Physiology
Hironori Fujita, Masayoshi Kawaguchi
Phyllotaxis, the arrangement of leaves on a plant stem, is well known because of its beautiful geometric configuration, which is derived from the constant spacing between leaf primordia. This phyllotaxis is established by mutual interaction between a diffusible plant hormone auxin and its efflux carrier PIN1, which cooperatively generate a regular pattern of auxin maxima, small regions with high auxin concentrations, leading to leaf primordia. However, the molecular mechanism of the regular pattern of auxin maxima is still largely unknown...
April 2018: PLoS Computational Biology
Masafumi Hidaka, Keita Kosaka, Saori Tsushima, Chiyoko Uchida, Katsuhiko Takahashi, Noriko Takahashi, Masayoshi Tsubuki, Yukihiko Hara, Takafumi Uchida
We searched for inhibitors against prolyl isomerase Pin1 in order to develop functional foods to prevent and cure various Pin1 related diseases such as cancer, diabetes, cardiovascular disease, Alzheimers's disease, and so on. We created a polyphenol library consisting of ingredients in healthy foods and beverages, since polyphenols like epigallocatechin gallate (EGCG) in green tea and 974B in brown algae had been identified as its Pin1 inhibitors. Several polyphenols such as EGCG derivatives, caffeic acid derivatives and tannic acid inhibited Pin1 activity...
March 30, 2018: Biochemical and Biophysical Research Communications
Daniel Pérez-Pascual, Doribet Jiménez-Guillen, Hernán Villanueva-Alonzo, Ramón Souza-Perera, Gregorio Godoy-Hernández, José Juan Zúñiga-Aguilar
Somatic embryogenesis receptor-like kinase 1 (SERK1) is a membrane receptor that might serve as common co-regulator of plant cell differentiation processes by forming heterodimers with specific receptor-like kinases. The Coffea canephora SERK1 homologue (CcSERK1) was cloned in this work, and its early function in the transcription of embryogenesis master genes and of genes encoding proteins involved in auxin metabolism was investigated by externally manipulating its expression in embryogenic leaf explants, before the appearance of embryogenic structures...
April 1, 2018: Physiologia Plantarum
Mingzhi Chen, Yang Xia, Yongfei Tan, Guojun Jiang, Hai Jin, Yijiang Chen
PIN1 is a peptidyl-prolyl cis/trans isomerase (PPIase) that controls cell fate by regulating multiple signal transduction pathways and is found to be overexpressed in a variety of malignant tumors. Herein, we found the expression of PIN1 is up-regulated while miRNA-370 (miR-370) down-regulated in both esophageal squamous-cell carcinoma (ESCC) tissues and cells. Transfection of miR-370 can significantly decrease PIN1 expression in targeting ESCC cells. Overexpression of miR-370 can induce decreased cell proliferation and cell cycle arrest, as well as increased apoptosis in ESCC cells, while this function can be significantly prevented by co-transfection of PIN1...
March 29, 2018: Gene
Cibele Tesser da Costa, Marcos Letaif Gaeta, Jorge Ernesto de Araujo Mariath, Remko Offringa, Arthur Germano Fett-Neto
Adventitious roots (ARs) emerge from stems, leaves or hypocotyls, being strategic for clonal propagation. ARs may develop spontaneously, upon environmental stress or hormonal treatment. Auxins strongly influence AR development (ARD), depending on concentration and kind. However, the role of different types of auxin is rarely compared at the molecular level. Rooting triggered by light exposure and flooding was examined in intact etiolated Arabidopsis thaliana hypocotyls treated with distinct auxin types. Morphological aspects, rooting-related gene expression profiles, and IAA immunolocalization were recorded...
March 21, 2018: Plant Physiology and Biochemistry: PPB
Suman K Samanta, Joomin Lee, Eun-Ryeong Hahm, Shivendra V Singh
We have reported previously that withaferin A (WA) prevents breast cancer development in mouse mammary tumor virus-neu (MMTV-neu) transgenic mice, but the mechanism is not fully understood. Unbiased proteomics of the mammary tumors from control- and WA-treated MMTV-neu mice revealed downregulation of peptidyl-prolyl cis/trans isomerase (Pin1) protein by WA administration. The present study extends these findings to elucidate the role of Pin1 in cancer chemopreventive mechanisms of WA. The mammary tumor level of Pin1 protein was lower by about 55% in WA-treated rats exposed to N-methyl-N-nitrosourea, compared to control...
March 30, 2018: Molecular Carcinogenesis
Mohamad Abu-Abied, Eduard Belausov, Sapir Hagay, Valera Peremyslov, Valerian Dolja, Einat Sadot
The interplay between myosin- and auxin-mediated processes was investigated by following root development in the triple myosin knockout mutant xi-k xi-1 xi-2 (3KO). It was found that the 3KO plants generated significantly more lateral and adventitious roots than the wild type plants or rescued plant line expressing functional myosin XI-K:YFP (3KOR). Using the auxin-dependent reporter DR5:venus, a significant change in the auxin gradient toward the root tip was found in 3KO plants, which correlated with the loss of polar localization of the auxin transporter PIN1 in the stele and with the increased number of the stele cells with oblique cell walls...
March 22, 2018: Journal of Experimental Botany
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