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https://www.readbyqxmd.com/read/28723063/using-cooperatively-folded-peptides-to-measure-interaction-energies-and-conformational-propensities
#1
Maziar S Ardejani, Evan T Powers, Jeffery W Kelly
The rates and equilibria of the folding of biopolymers are determined by the conformational preferences of the subunits that make up the sequence of the biopolymer and by the interactions that are formed in the folded state in aqueous solution. Because of the centrality of these processes to life, quantifying conformational propensities and interaction strengths is vitally important to understanding biology. In this Account, we describe our use of peptide model systems that fold cooperatively yet are small enough to be chemically synthesized to measure such quantities...
July 19, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28708092/the-exact-nuclear-overhauser-enhancement-recent-advances
#2
REVIEW
Parker J Nichols, Alexandra Born, Morkos A Henen, Dean Strotz, Julien Orts, Simon Olsson, Peter Güntert, Celestine N Chi, Beat Vögeli
Although often depicted as rigid structures, proteins are highly dynamic systems, whose motions are essential to their functions. Despite this, it is difficult to investigate protein dynamics due to the rapid timescale at which they sample their conformational space, leading most NMR-determined structures to represent only an averaged snapshot of the dynamic picture. While NMR relaxation measurements can help to determine local dynamics, it is difficult to detect translational or concerted motion, and only recently have significant advances been made to make it possible to acquire a more holistic representation of the dynamics and structural landscapes of proteins...
July 14, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28706471/scalable-text-mining-assisted-curation-of-post-translationally-modified-proteoforms-in-the-protein-ontology
#3
Karen E Ross, Darren A Natale, Cecilia Arighi, Sheng-Chih Chen, Hongzhan Huang, Gang Li, Jia Ren, Michael Wang, K Vijay-Shanker, Cathy H Wu
The Protein Ontology (PRO) defines protein classes and their interrelationships from the family to the protein form (proteoform) level within and across species. One of the unique contributions of PRO is its representation of post-translationally modified (PTM) proteoforms. However, progress in adding PTM proteoform classes to PRO has been relatively slow due to the extensive manual curation effort required. Here we report an automated pipeline for creation of PTM proteoform classes that leverages two phosphorylation-focused text mining tools (RLIMS-P, which detects mentions of kinases, substrates, and phosphorylation sites, and eFIP, which detects phosphorylation-dependent protein-protein interactions (PPIs)) and our integrated PTM database, iPTMnet...
August 2016: CEUR Workshop Proceedings
https://www.readbyqxmd.com/read/28693423/indole-3-butyric-acid-promotes-adventitious-rooting-in-arabidopsis-thaliana-thin-cell-layers-by-conversion-into-indole-3-acetic-acid-and-stimulation-of-anthranilate-synthase-activity
#4
L Fattorini, A Veloccia, F Della Rovere, S D'Angeli, G Falasca, M M Altamura
BACKGROUND: Indole-3-acetic acid (IAA), and its precursor indole-3-butyric acid (IBA), control adventitious root (AR) formation in planta. Adventitious roots are also crucial for propagation via cuttings. However, IBA role(s) is/are still far to be elucidated. In Arabidopsis thaliana stem cuttings, 10 μM IBA is more AR-inductive than 10 μM IAA, and, in thin cell layers (TCLs), IBA induces ARs when combined with 0.1 μM kinetin (Kin). It is unknown whether arabidopsis TCLs produce ARs under IBA alone (10 μM) or IAA alone (10 μM), and whether they contain endogenous IAA/IBA at culture onset, possibly interfering with the exogenous IBA/IAA input...
July 11, 2017: BMC Plant Biology
https://www.readbyqxmd.com/read/28687624/patellins-are-regulators-of-auxin-mediated-pin1-relocation-and-plant-development-in-arabidopsis-thaliana
#5
Ricardo Tejos, Cecilia Rodriguez-Furlan, Maciej Adamowski, Michael Sauer, Lorena Norambuena, Jiří Friml
Coordinated cell polarization in developing tissues is a recurrent theme in multicellular organisms. In plants, a directional distribution of the plant hormone auxin is at the core of many developmental programs. A feedback regulation of auxin on the polarized localization of PIN auxin transporters in individual cells has been proposed as a self-organizing mechanism for coordinated tissue polarization, but the molecular mechanisms linking auxin signalling to PIN-dependent auxin transport remain unknown. We performed a microarray-based approach to find regulators of the auxin-induced PIN relocation in the Arabidopsis thaliana root...
July 7, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28678584/inhibition-of-cdk-mediated-smad3-phosphorylation-reduces-the-pin1-smad3-interaction-and-aggressiveness-of-triple-negative-breast-cancer-cells
#6
Alexandra L Thomas, Hanne Lind, Angela Hong, Danijela Dokic, Kailey Oppat, Elana Rosenthal, Amina Guo, Aaron Thomas, Randala Hamden, Jacqueline S Jeruss
Triple negative breast cancer (TNBC) is a highly aggressive breast cancer subtype that lacks effective targeted therapies. Although TNBC is not defined by specific therapeutic targets, a subset of patients have tumors that overexpress cyclins. High cyclin D/E expression catalyzes CDK4/2 activity. In turn, CDK4/2 can non-canonically phosphorylate Smad3, a key TGFβ signaling intermediate, and this phosphorylation has been associated with the shift from tumor-suppressive to oncogenic TGFβ pathway action in breast oncogenesis...
July 5, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28676695/functional-pin1-promoter-polymorphisms-associated-with-risk-of-nasopharyngeal-carcinoma-in-southern-chinese-populations
#7
Liuyan Zeng, Shengqun Luo, Xin Li, Mengxuan Lu, Huahui Li, Tong Li, Guanhua Wang, Xiaoming Lyu, Wenrui Jia, Zigang Dong, Qiang Jiang, Zhihua Shen, Guo-Liang Huang, Zhiwei He
Our previous work reported the association between two single nucleotide polymorphisms (SNPs) in PIN1 promoter and nasopharyngeal carcinoma (NPC) risk with a small sample size in a low incidence area. This study investigated the association between the two SNPs and NPC risk in 733 patients and 895 controls from a high incidence area. The results indicated the genotype and allele frequencies of -842G > C and -667C > T were both significantly different between patients and controls even using the resampling statistics...
July 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28674551/high-mir156-expression-is-required-for-auxin-induced-adventitious-root-formation-via-mxspl26-independent-of-pins-and-arfs-in-malus-xiaojinensis
#8
Xiaozhao Xu, Xu Li, Xingwang Hu, Ting Wu, Yi Wang, Xuefeng Xu, Xinzhong Zhang, Zhenhai Han
Adventitious root formation is essential for the vegetative propagation of perennial woody plants. During the juvenile-to-adult phase change mediated by the microRNA156 (miR156), the adventitious rooting ability decreases dramatically in many species, including apple rootstocks. However, the mechanism underlying how miR156 affects adventitious root formation is unclear. In the present study, we showed that in the presence of the synthetic auxin indole-3-butyric acid (IBA), semi-lignified leafy cuttings from juvenile phase (Mx-J) and rejuvenated (Mx-R) Malus xiaojinensis trees exhibited significantly higher expression of miR156, PIN-FORMED1 (PIN1), PIN10, and rootless concerning crown and seminal roots-like (RTCS-like) genes, thus resulting in higher adventitious rooting ability than those from adult phase (Mx-A) trees...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28673242/the-pin-gene-family-in-cotton-gossypium-hirsutum-genome-wide-identification-and-gene-expression-analyses-during-root-development-and-abiotic-stress-responses
#9
Peng He, Peng Zhao, Limin Wang, Yuzhou Zhang, Xiaosi Wang, Hui Xiao, Jianing Yu, Guanghui Xiao
BACKGROUND: Cell elongation and expansion are significant contributors to plant growth and morphogenesis, and are often regulated by environmental cues and endogenous hormones. Auxin is one of the most important phytohormones involved in the regulation of plant growth and development and plays key roles in plant cell expansion and elongation. Cotton fiber cells are a model system for studying cell elongation due to their large size. Cotton is also the world's most utilized crop for the production of natural fibers for textile and garment industries, and targeted expression of the IAA biosynthetic gene iaaM increased cotton fiber initiation...
July 3, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28671058/dual-roles-of-pin1-in-cancer-development-and-progression
#10
Hyeong-Jun Han, Bu Young Choi, Young-Joon Surh
Pin 1 is a unique peptidyl-prolyl cis/trans isomerase (PPIase) that catalyzes the cis/trans isomerization of peptidyl-prolyl peptide bonds of its substrate proteins by binding to their specific phosphorylated Ser/Thr-Pro (pSer/Thr-Pro) motifs. This alters the conformation of target proteins and consequently affects their stability, intracellular localization, and/or biological functions. The abnormal overexpression of Pin1 is observed in some malignancies, which is associated with cancer cell proliferation, migration and invasion...
July 3, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28670853/the-pathological-roles-of-ndrg2-in-alzheimer-s-disease-a-study-using-animal-models-and-appwt-overexpressed-cells
#11
Xian-Fang Rong, Ying-Ni Sun, Dong-Mei Liu, Hua-Jing Yin, Ying Peng, Shao-Feng Xu, Ling Wang, Xiao-Liang Wang
AIMS: To investigate the roles of N-myc downstream-regulated gene 2 (NDRG2) in the pathology of aging and neurodegenerative disease such as Alzheimer's disease (AD). RESULTS: In this study, we confirmed the upregulation of NDRG2 in the brains of aging and AD animal models. To explore the role of NDRG2 in the pathology of AD at molecular level, we conducted a cell-based assay of highly expressed wild-type human APP695 SK-N-SH cells (SK-N-SH APPwt). By silencing and overexpressing gene of NDRG2, we demonstrated that NDRG2-mediated increase in Aβ1-42 was through the pathways of BACE1 and GGA3...
July 2, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28660363/adaptation-of-root-growth-to-increased-ambient-temperature-requires-auxin-and-ethylene-coordination-in-arabidopsis
#12
Qionghui Fei, Shaodong Wei, Zhaoyang Zhou, Huanhuan Gao, Xiaofeng Li
A fresh look at the roles of auxin, ethylene, and polar auxin transport during the plant root growth response to warmer ambient temperature (AT). The ambient temperature (AT) affects plant growth and development. Plants can sense changes in the AT, but how this change is transduced into a plant root growth response is still relatively unclear. Here, we found that the Arabidopsis ckrc1-1 mutant is sensitive to higher AT. At 27 °C, the ckrc1-1 root length is significantly shortened and the root gravity defect is enhanced, changes that can be restored with addition of 1-naphthaleneacetic acid, but not indole-3-acetic acid (IAA)...
June 28, 2017: Plant Cell Reports
https://www.readbyqxmd.com/read/28617332/dynamic-allostery-modulates-catalytic-activity-by-modifying-the-hydrogen-bonding-network-in-the-catalytic-site-of-human-pin1
#13
Jing Wang, Ryosuke Kawasaki, Jun-Ichi Uewaki, Arif U R Rashid, Naoya Tochio, Shin-Ichi Tate
Allosteric communication among domains in modular proteins consisting of flexibly linked domains with complimentary roles remains poorly understood. To understand how complementary domains communicate, we have studied human Pin1, a representative modular protein with two domains mutually tethered by a flexible linker: a WW domain for substrate recognition and a peptidyl-prolyl isomerase (PPIase) domain. Previous studies of Pin1 showed that physical contact between the domains causes dynamic allostery by reducing conformation dynamics in the catalytic domain, which compensates for the entropy costs of substrate binding to the catalytic site and thus increases catalytic activity...
June 15, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28617078/interplay-between-notch-and-p53-promotes-neuronal-cell-death-in-ischemic-stroke
#14
Priyanka Balaganapathy, Sang-Ha Baik, Karthik Mallilankaraman, Christopher G Sobey, Dong-Gyu Jo, Thiruma V Arumugam
Stroke is the world's second leading cause of mortality, with a high incidence of morbidity. Numerous neuronal membrane receptors are activated by endogenous ligands and may contribute to infarct development. Notch is a well-characterized membrane receptor involved in cell differentiation and proliferation, and now shown to play a pivotal role in cell death during ischemic stroke. Blockade of Notch signaling by inhibition of γ-secretase, an enzyme that generates the active form of Notch, is neuroprotective following stroke...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28598431/a-covalent-pin1-inhibitor-selectively-targets-cancer-cells-by-a-dual-mechanism-of-action
#15
Elena Campaner, Alessandra Rustighi, Alessandro Zannini, Alberto Cristiani, Silvano Piazza, Yari Ciani, Ori Kalid, Gali Golan, Erkan Baloglu, Sharon Shacham, Barbara Valsasina, Ulisse Cucchi, Agnese Chiara Pippione, Marco Lucio Lolli, Barbara Giabbai, Paola Storici, Paolo Carloni, Giulia Rossetti, Federica Benvenuti, Ezia Bello, Maurizio D'Incalci, Elisa Cappuzzello, Antonio Rosato, Giannino Del Sal
The prolyl isomerase PIN1, a critical modifier of multiple signalling pathways, is overexpressed in the majority of cancers and its activity strongly contributes to tumour initiation and progression. Inactivation of PIN1 function conversely curbs tumour growth and cancer stem cell expansion, restores chemosensitivity and blocks metastatic spread, thus providing the rationale for a therapeutic strategy based on PIN1 inhibition. Notwithstanding, potent PIN1 inhibitors are still missing from the arsenal of anti-cancer drugs...
June 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28592245/in-silico-identification-of-potential-key-regulatory-factors-in-smoking-induced-lung-cancer
#16
Salem A El-Aarag, Amal Mahmoud, Medhat H Hashem, Hatem Abd Elkader, Alaa E Hemeida, Mahmoud ElHefnawi
BACKGROUND: Lung cancer is a leading cause of cancer-related death worldwide and is the most commonly diagnosed cancer. Like other cancers, it is a complex and highly heterogeneous disease involving multiple signaling pathways. Identifying potential therapeutic targets is critical for the development of effective treatment strategies. METHODS: We used a systems biology approach to identify potential key regulatory factors in smoking-induced lung cancer. We first identified genes that were differentially expressed between smokers with normal lungs and those with cancerous lungs, then integrated these differentially expressed genes (DEGs) with data from a protein-protein interaction database to build a network model with functional modules for pathway analysis...
June 7, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/28575401/localization-of-arabidopsis-forked1-to-a-raba-positive-compartment-suggests-a-role-in-secretion
#17
Neema Prabhakaran Mariyamma, Hongwei Hou, Francine M Carland, Timothy Nelson, Elizabeth A Schultz
When FORKED1 (FKD1) is mutated, asymmetric localization of PINFORMED1 (PIN1), particularly to the apical side of cells, fails to occur properly in developing veins, resulting in an open vein pattern. FKD1 encodes a protein with a Pleckstrin homology-like (PL) domain, suggesting interaction with phosphoinositides. FKD1 has been previously found to interact with an ADP ribosylation factor GTPase-activating protein (ARF-GAP) important for vein patterning, SCARFACE/VAN3 (SFC). We find that FKD1-green fluorescent protein (GFP) localizes to the plasma membrane and to punctae labeled by SFC-yellow fluorescent protein (YFP)...
June 1, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28566287/the-prolyl-isomerase-pin1-increases-%C3%AE-cell-proliferation-and-enhances-insulin-secretion
#18
Yusuke Nakatsu, Keiichi Mori, Yasuka Matsunaga, Takeshi Yamamotoya, Koji Ueda, Yuki Inoue, Keiko Mitsuzaki-Miyoshi, Hideyuki Sakoda, Midori Fujishiro, Suguru Yamaguchi, Akifumi Kushiyama, Hiraku Ono, Hisamitsu Ishihara, Tomoichiro Asano
The prolyl isomerase Pin1 binds to the phosphorylated Ser/Thr-Pro motif of target proteins and enhances their cis-trans conversion. This report is the first to show that Pin1 expression in pancreatic β cells is markedly elevated by high-fat diet feeding and in ob/ob mice. To elucidate the role of Pin1 in pancreatic β cells, we generated β-cell-specific Pin1 KO (βPin1 KO) mice. These mutant mice showed exacerbation of glucose intolerance but had normal insulin sensitivity. We identified two independent factors underlying impaired insulin secretion in the βPin1 KO mice...
July 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28556372/plant-plant-interactions-influence-developmental-phase-transitions-grain-productivity-and-root-system-architecture-in-arabidopsis-via-auxin-and-pft1-med25-signaling
#19
Edith Muñoz-Parra, Ramón Pelagio-Flores, Javier Raya-González, Guadalupe Salmerón-Barrera, León Francisco Ruiz-Herrera, Eduardo Valencia-Cantero, José López-Bucio
Transcriptional regulation of gene expression influences plant growth, environmental interactions, and plant-plant communication. Here, we report that population density is a key factor for plant productivity and a major root architectural determinant in Arabidopsis thaliana. When grown in soil at varied densities from 1 to 32 plants, high number of individuals decreased stem growth and accelerated senescence, which negatively correlated with total plant biomass and seed production at the completion of the life cycle...
May 27, 2017: Plant, Cell & Environment
https://www.readbyqxmd.com/read/28533744/pin1-modulates-huntingtin-levels-and-aggregate-accumulation-an-in-vitro-model
#20
Alisia Carnemolla, Silvia Michelazzi, Elena Agostoni
Huntington's disease (HD) is a dominantly inherited neurodegenerative disorder characterized by a polyglutamine expansion within the N-terminal region of huntingtin protein (HTT). Cellular mechanisms promoting mutant huntingtin (mHTT) clearance are of great interest in HD pathology as they can lower the level of the mutant protein and its toxic aggregated species, thus affecting disease onset and progression. We have previously shown that the prolyl-isomerase PIN1 represents a promising negative regulator of mHTT aggregate accumulation using a genetically precise HD mouse model, namely Hdh(Q111) mice...
2017: Frontiers in Cellular Neuroscience
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