Read by QxMD icon Read


Yuan-Chin Lee, Ying-Jung Chen, Chia-Hui Huang, Long-Sen Chang
Previous studies have attributed the anticancer activity of amsacrine to its inhibitory effect on topoisomerase II. However, 9-aminoacridine derivatives, which have the same structural scaffold as amsacrine, induce cancer cell apoptosis by altering the expression of BCL2 family proteins. Therefore, in the present study, we assessed whether BCL2 family proteins mediated the cytotoxic effects of amsacrine on human leukemia U937 cells. Amsacrine-induced apoptosis of U937 cells was characterized by caspase-9 and caspase-3 activation, increased intracellular Ca(2+) concentration, mitochondrial depolarization, and MCL1 down-regulation...
October 19, 2016: Apoptosis: An International Journal on Programmed Cell Death
Mara Cucinotta, Silvia Manrique, Andrea Guazzotti, Nadia E Quadrelli, Marta A Mendes, Eva Benkova, Lucia Colombo
The developmental program of the pistil is under the control of both auxin and cytokinin, which crosstalk converges on the regulation of the auxin carrier PIN-FORMED 1 (PIN1). Here we show that in the triple transcription factor mutant cytokinin response factor 2 (crf2) crf3 crf6 both pistil length and ovule number were reduced. PIN1 expression was also lower in the triple mutant and the phenotypes couldn't be rescued by exogenous cytokinin application. pin1 complementation studies using genomic PIN1 constructs showed that the pistil phenotypes were only rescued when the PCRE1 domain, to which CRFs bind, was present...
October 13, 2016: Development
Daeeun Ki, Daisuke Sasayama, Hyung-Taeg Cho
Asymmetrically localized PIN-FORMED (PIN) auxin efflux carriers play key roles in regulating directional intercellular auxin movement, generating local auxin gradients, and diverse auxin-mediated growth and development. The polar localization of PINs is controlled by phosphorylation in the central hydrophilic loop (HL) of PINs. Although the M3 phosphorylation site, including phosphorylatable 5 Ser/Thr residues, is conserved among long HL-PINs, its native role has only been characterized in PIN3. In this study, we examined the role of M3 phosphorylation site of PIN1, PIN2, and PIN7 in intracellular trafficking, phosphorylation, and biological functions of those PINs in their native expressing tissues...
2016: Frontiers in Plant Science
Laura Nogués, Clara Reglero, Verónica Rivas, Alicia Salcedo, Vanesa Lafarga, Maria Neves, Paula Ramos, Marta Mendiola, Alberto Berjón, Kostas Stamatakis, Xiao Zhen Zhou, Kun Ping Lu, David Hardisson, Federico Mayor, Petronila Penela
In addition to oncogenic drivers, signaling nodes can critically modulate cancer-related cellular networks to strength tumor hallmarks. We identify G-protein-coupled receptor kinase 2 (GRK2) as a relevant player in breast cancer. GRK2 is up-regulated in breast cancer cell lines, in spontaneous tumors in mice, and in a proportion of invasive ductal carcinoma patients. Increased GRK2 functionality promotes the phosphorylation and activation of the Histone Deacetylase 6 (HDAC6) leading to de-acetylation of the Prolyl Isomerase Pin1, a central modulator of tumor progression, thereby enhancing its stability and functional interaction with key mitotic regulators...
October 1, 2016: EBioMedicine
Michaela Matthes, Ramón A Torres-Ruiz
Several observations suggest that the micronutrient boron (B) has a stabilizing role in the plasma membrane (PM), supporting functions in PM-linked (hormone) signalling processes. However, this role is poorly characterized. This study shows, that boronic acids, specific competitors of B, induce phenocopies of the Arabidopsis thaliana rootless pattern mutant monopteros At least in part, this is caused by phenylboronic acid (PBA)-induced internalisation of the membrane-localized auxin efflux carrier PINFORMED1 (PIN1) in the early embryo...
October 3, 2016: Development
Hailong Zhao, Guonan Cui, Jing Jin, Xiaoguang Chen, Bailing Xu
Pin1 (Protein interacting with NIMA1) is a peptidyl prolyl cis-trans isomerase (PPIase) which specifically catalyze the conformational conversion of the amide bond of pSer/Thr-Pro motifs in its substrate proteins and is a novel promising anticancer target. A series of new thiazole derivatives were designed and synthesized, and their inhibitory activities were measured against human Pin1 using a protease-coupled enzyme assay. Of all the tested compounds, a number of thiazole derivatives bearing an oxalic acid group at 4-position were found to be potent Pin1 inhibitors with IC50 values at low micromolar level...
September 21, 2016: Bioorganic & Medicinal Chemistry
Ewa Mazur, Eva Benková, Jiří Friml
Synchronized tissue polarization during regeneration or de novo vascular tissue formation is a plant-specific example of intercellular communication and coordinated development. According to the canalization hypothesis, the plant hormone auxin serves as polarizing signal that mediates directional channel formation underlying the spatio-temporal vasculature patterning. A necessary part of canalization is a positive feedback between auxin signaling and polarity of the intercellular auxin flow. The cellular and molecular mechanisms of this process are still poorly understood, not the least, because of a lack of a suitable model system...
2016: Scientific Reports
Xue Liu, Ershun Liang, Xiuhui Song, Zhanhui Du, Yun Zhang, Yuxia Zhao
Therapeutic management of diabetic myocardial fibrosis remains an unsolved clinical problem. Pin1, a peptidyl-prolyl isomerase, impacts diverse cellular processes and plays a pivotal role in regulating cardiac pathophysiology. Here we investigate the potential mechanism of action of Pin1 and its role in diabetes-induced myocardial fibrosis and dysfunction in mice. Cardiac Pin1, transforming growth factor β1 (TGF-β1), α-smooth muscle actin (α-SMA) and extracellular matrix deposits (collagen I and III) are found to be increased in diabetic mice, which are effectively prevented by Pin1 inhibition by juglone...
October 7, 2016: Biochemical and Biophysical Research Communications
Tomasz Nodzyński, Steffen Vanneste, Marta Zwiewka, Markéta Pernisová, Jan Hejátko, Jiří Friml
Auxin directs plant ontogenesis via differential accumulation within tissues depending largely on the activity of PIN proteins that mediate auxin efflux from cells and thus directional cell-to-cell transport. Regardless of the developmental importance of PINs the structure of these transporters is poorly characterised. Here, we present experimental data concerning protein topology of plasma membrane-localised PINs. Utilizing techniques based on pH-dependant quenching of fluorescent reporters combined with immunolocalization techniques we mapped PIN membrane topology cross-validating our results using available topology modelling software...
September 10, 2016: Molecular Plant
Weiyan Jia, Baohua Li, Shujia Li, Yan Liang, Xiaowei Wu, Mei Ma, Jiyao Wang, Jin Gao, Yueyue Cai, Yuanya Zhang, Yingchun Wang, Jiayang Li, Yonghong Wang
Emerging evidences exhibit that mitogen-activated protein kinase (MAPK/MPK) signaling pathways are connected with many aspects of plant development. The complexity of MAPK cascades raises challenges not only to identify the MAPK module in planta but also to define the specific role of an individual module. So far, our knowledge of MAPK signaling has been largely restricted to a small subset of MAPK cascades. Our previous study has characterized an Arabidopsis bushy and dwarf1 (bud1) mutant, in which the MAP Kinase Kinase 7 (MKK7) was constitutively activated, resulting in multiple phenotypic alterations...
September 2016: PLoS Biology
Yusuke Nakatsu, Yasuka Matsunaga, Takeshi Yamamotoya, Koji Ueda, Yuki Inoue, Keiichi Mori, Hideyuki Sakoda, Midori Fujishiro, Hiraku Ono, Akifumi Kushiyama, Tomoichiro Asano
Prolyl isomerases are divided into three groups, the FKBP family, Cyclophilin and the Parvulin family (Pin1 and Par14). Among these isomerases, Pin1 is a unique prolyl isomerase binding to the motif including pSer/pThr-Pro that is phosphorylated by kinases. Once bound, Pin1 modulates the enzymatic activity, protein stability or subcellular localization of target proteins by changing the cis- and trans-formations of proline. Several studies have examined the roles of Pin1 in the pathogenesis of cancers and Alzheimer's disease...
2016: International Journal of Molecular Sciences
F Baruffaldi, D Montarras, V Basile, L De Feo, S Badodi, M Ganassi, R Battini, C Nicoletti, C Imbriano, A Musarò, S Molinari
The transcription factor MEF2C (Myocyte Enhancer Factor 2C) plays an established role in the early steps of myogenic differentiation. However, the involvement of MEF2C in adult myogenesis and in muscle regeneration has not yet been systematically investigated. Alternative splicing of mammalian MEF2C transcripts gives rise to two mutually exclusive protein variants: MEF2Cα2 which exerts a positive control of myogenic differentiation, and MEF2Cα1, in which the α1 domain acts as trans-repressor of the MEF2C pro-differentiation activity itself...
September 10, 2016: Stem Cells
María Jesús Marcote, Gloria Sancho-Andrés, Esther Soriano-Ortega, Fernando Aniento
PIN-FORMED (PIN) family proteins direct polar auxin transport based on their asymmetric (polar) localization at the plasma membrane. In the case of PIN1, it mainly localizes to the basal (rootward) plasma membrane domain of stele cells in root meristems. Vesicular trafficking events, such as clathrin-dependent PIN1 endocytosis and polar recycling, are probably the main determinants for PIN1 polar localization. However, very little is known about the signals which may be involved in binding the μ-adaptin subunit of clathrin adaptor complexes (APs) for sorting of PIN1 within clathrin-coated vesicles, which can determine its trafficking and localization...
August 2, 2016: Plant Signaling & Behavior
Irena Týcová, Sylvie Dusilová Sulková, Jitka Štěpánková, Zdeněk Krejčík, Michaela Dostálová Merkerová, Viktor Stránecký, Petra Hrubá, Eva Girmanová, Marek Černoch, Květoslav Lipár, Tomáš Marada, Ctibor Povýšil, Ondřej Viklický
Secondary hyperparathyroidism is a well-known complication of end-stage renal disease (ESRD). Both nodular and diffuse parathyroid hyperplasia occur in ESRD patients. However, their distinct molecular mechanisms remain poorly understood. Parathyroid tissue obtained from ESRD patients who had undergone parathyroidectomy was used for Illumina transcriptome screening and subsequently for discriminatory gene analysis, pathway mapping, and gene annotation enrichment analysis. Results were further validated using quantitative RT-PCR on the independent larger cohort...
October 1, 2016: American Journal of Physiology. Endocrinology and Metabolism
Jing-Yi Chen, You-Syuan Lai, Hui-Jen Tsai, Cheng-Chin Kuo, B Linju Yen, Su-Peng Yeh, H Sunny Sun, Wen-Chun Hung
Mutations of isocitrate dehydrogenase 1 (IDH1) and IDH2 in acute myeloid leukemia (AML) cells produce the oncometabolite R-2-hydroxyglutarate (R-2HG) to induce epigenetic alteration and block hematopoietic differentiation. However, the effect of R-2HG released by IDH-mutated AML cells on the bone marrow microenvironment is unclear. Here, we report that R-2HG induces IκB kinase-independent activation of NF-κB in bone marrow stromal cells. R-2HG acts via a reactive oxygen species/extracellular signal-regulated kinase (ERK)-dependent pathway to phosphorylate NF-κB on the Thr254 residue...
2016: Scientific Reports
Sang-Hyun Min, Xiao Zhen Zhou, Kun Ping Lu
Protein phosphorylation and post-phosphorylation events regulate many cellular signaling pathways. Peptidyl-prolyl isomerase (Pin1) is the only peptidyl-prolyl cis/trans isomerase that interacts with numerous oncogenic or tumor suppressive phosphorylated proteins, causes conformational changes in target proteins, and eventually regulates the activities of such proteins. These alterations in activity play a pivotal role in tumorigenesis. Since Pin1 is overexpressed and/or activated in various types of cancers, and the dysregulation of proline-directed phosphorylation contributes to tumorigenesis, Pin1 represents an attractive target for cancer therapy...
August 29, 2016: Archives of Pharmacal Research
Jens Milbradt, Corina Hutterer, Hanife Bahsi, Sabrina Wagner, Eric Sonntag, Anselm H C Horn, Benedikt B Kaufer, Yasuko Mori, Heinrich Sticht, Torgils Fossen, Manfred Marschall
The nuclear lamina lines the inner nuclear membrane providing a structural framework for the nucleus. Cellular processes, such as nuclear envelope breakdown during mitosis or nuclear export of large ribonucleoprotein complexes, are functionally linked to the disassembly of the nuclear lamina. In general, lamina disassembly is mediated by phosphorylation, but the precise molecular mechanism is still not completely understood. Recently, we suggested a novel mechanism for lamina disassembly during the nuclear egress of herpesviral capsids which involves the cellular isomerase Pin1...
August 2016: PLoS Pathogens
Ciera C Martinez, Daniel Koenig, Daniel H Chitwood, Neelima R Sinha
The spatiotemporal localization of the plant hormone auxin acts as a positional cue during early leaf and flower organogenesis. One of the main contributors to auxin localization is the auxin efflux carrier PIN-FORMED1 (PIN1). Phylogenetic analysis has revealed that PIN1 genes are split into two sister clades; PIN1 and the relatively uncharacterized Sister-Of-PIN1 (SoPIN1). In this paper we identify entire-2 as a loss-of-function SlSoPIN1a (Solyc10g078370) mutant in Solanum lycopersicum. The entire-2 plants are unable to specify proper leaf initiation leading to a frequent switch from the wild type spiral phyllotactic pattern to distichous and decussate patterns...
August 20, 2016: Developmental Biology
Jia-Gang Wang, Chong Feng, Hai-Hong Liu, Fu-Rong Ge, Sha Li, Hong-Ju Li, Yan Zhang
Planar morphogenesis, a distinct feature of multicellular organisms, is crucial for the development of ovule, progenitor of seeds. Both receptor-like kinases (RLKs) such as STRUBBELIG (SUB) and auxin gradient mediated by PIN-FORMED1 (PIN1) play instructive roles in this process. Fine-tuned intercellular communications between different cell layers during ovule development demands dynamic membrane distribution of these cell-surface proteins, presumably through vesicle-mediated sorting. However, the way it's achieved and the trafficking routes involved are obscure...
August 2016: PLoS Genetics
Md Aminul Islam, Christine Große-Brinkhaus, Maren Julia Pröll, Muhammad Jasim Uddin, Sharmin Aqter Rony, Dawit Tesfaye, Ernst Tholen, Michael Hölker, Karl Schellander, Christiane Neuhoff
BACKGROUND: Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically important viral diseases affecting swine industry worldwide. Despite routine farm vaccination, effective control strategies for PRRS remained elusive which underscores the need for in-depth studies to gain insight into the host immune response to vaccines. The current study aimed to investigate transcriptional responses to PRRS Virus (PRRSV) vaccine in the peripheral blood mononuclear cells (PBMCs) within 3 days following vaccination in German Landrace pigs...
2016: BMC Genomics
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"