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Ulrich Gergs, Theresa Trapp, Hasan Bushnaq, Andreas Simm, Rolf-Edgar Silber, Joachim Neumann
Heart failure and aging of the heart show many similarities regarding hemodynamic and biochemical parameters. There is evidence that heart failure in experimental animals and humans is accompanied and possibly exacerbated by increased activity of protein phosphatase (PP) 1 and/or 2A. Here, we wanted to study the age-dependent protein expression of major members of the protein phosphatase family in human hearts. Right atrial samples were obtained during bypass surgery. Patients ( n =60) were suffering from chronic coronary artery disease (CCS 2-3; New York Heart Association (NYHA) stage 1-3)...
2019: Advances in Medicine
Sandra Loera-Serna, Jorge Flores, Alejandra M Navarrete-López, Jorge Noé Díaz de Leon, Hiram I Beltran
HKUST-1 was employed as an interaction matrix for fundamental loading studies of anthraquinone dyes. Chosen dyes were alizarin (A), alizarin S (AS), disperse blue 1 (B1), disperse blue 3 (B3), disperse blue 56 (B56) and purpurin (P). All materials were characterized by XRD, FTIR, TGA and SEM. Hence interaction of dyes with the framework was characterized by theoretical-experimental differential analysis. One pot loading strategy resulted more efficient to scavenge dyes, reached 100% for B56 using 50 mg·L-1...
January 4, 2019: Chemistry: a European Journal
Sara Reynhout, Sandra Jansen, Dorien Haesen, Siska van Belle, Sonja A de Munnik, Ernie M H F Bongers, Jolanda H Schieving, Carlo Marcelis, Jeanne Amiel, Marlène Rio, Heather Mclaughlin, Roger Ladda, Susan Sell, Marjolein Kriek, Cacha M P C D Peeters-Scholte, Paulien A Terhal, Koen L van Gassen, Nienke Verbeek, Sonja Henry, Jessica Scott Schwoerer, Saleem Malik, Nicole Revencu, Carlos R Ferreira, Ellen Macnamara, Hilde M H Braakman, Elise Brimble, Maura R Z Ruznikov, Matias Wagner, Philip Harrer, Dagmar Wieczorek, Alma Kuechler, Barak Tziperman, Ortal Barel, Bert B A de Vries, Christopher T Gordon, Veerle Janssens, Lisenka E L M Vissers
Type 2A protein phosphatases (PP2As) are highly expressed in the brain and regulate neuronal signaling by catalyzing phospho-Ser/Thr dephosphorylations in diverse substrates. PP2A holoenzymes comprise catalytic C-, scaffolding A-, and regulatory B-type subunits, which determine substrate specificity and physiological function. Interestingly, de novo mutations in genes encoding A- and B-type subunits have recently been implicated in intellectual disability (ID) and developmental delay (DD). We now report 16 individuals with mild to profound ID and DD and a de novo mutation in PPP2CA, encoding the catalytic Cα subunit...
December 21, 2018: American Journal of Human Genetics
Huan He, Marie-Pierre Brenier-Pinchart, Laurence Braun, Alexandra Kraut, Bastien Touquet, Yohann Couté, Isabelle Tardieux, Mohamed-Ali Hakimi, Alexandre Bougdour
The intracellular parasite Toxoplasma gondii, hijacks evolutionarily conserved host processes by delivering effector proteins into the host cell that shift gene expression in a timely fashion. We identified a parasite dense granule protein as GRA18 that once released in the host cell cytoplasm forms versatile complexes with regulatory elements of the β-catenin destruction complex. By interacting with GSK3/PP2A-B56, GRA18 drives β-catenin up-regulation and the downstream effects on host cell gene expression...
October 15, 2018: ELife
Zhongqi Chen, Ningfei Ji, Zhengxia Wang, Chaojie Wu, Zhixiao Sun, Yan Li, Fan Hu, Zibin Wang, Mao Huang, Mingshun Zhang
Accumulating evidence indicates that fine particulate matter (PM2.5) exposure is associated with many cardiopulmonary diseases, particularly lung carcinoma. Nevertheless, the underlying biological mechanisms by which PM2.5 exposure initiates and aggravates lung carcinoma remain elusive. In the present study, we collected PM2.5 in Nanjing and explored the mechanisms underlying the oncogenic roles of PM2.5 in the murine lung carcinoma cell line LLC in vitro and in vivo . PM2.5 was closely attached to and internalized by lung cancer cells...
December 1, 2018: Journal of Biomedical Nanotechnology
Ryotaro Yabe, Shunya Tsuji, Satoru Mochida, Tsuyoshi Ikehara, Tatsuya Usui, Takashi Ohama, Koichi Sato
Reversible methyl-esterification (methylation) of Leu309 in the protein phosphatase 2A catalytic subunit (PP2Ac) is essential for proper biogenesis of the PP2A holoenzyme. Accumulating evidence links PP2Ac methylation to diseases, including cancer and neurodegenerative disorders. Protein phosphatase methyl-esterase (PME-1) specifically catalyzes PP2Ac demethylation. We demonstrate that PP2Ac is demethylated in cell extracts even at 0 °C unless prevented by a PME-1 methyl-esterase inhibitor. This promotes dissociation of PP2A heterotrimers with B55 or PR72 subunits, but not those with B56 subunits...
September 2018: FEBS Open Bio
Jialu Li, Hao Ren, Xiaoqin Zou, Kun Cai, Nian Zhao, Guangshan Zhu
This work reports a new synthesis strategy called hard-template synthesis to create hierarchical pores in porous organic framework materials. Two different mesoporous silicas (SBA-15 and B56-E-20) were used as the hard templates and biphenyl was employed as the single organic precursor. PAF-45 was prepared by in situ coupling biphenyl within the voids of mesoporous silica. After etching silica, controlled mesopores with sizes ranging from 3 to 10 nm were generated and microporosity was inherited as well in the mesoporous PAF-45HX materials...
July 24, 2018: Chemical Communications: Chem Comm
Adrian T Saurin
Multiple kinases and phosphatases act on the kinetochore to control chromosome segregation: Aurora B, Mps1, Bub1, Plk1, Cdk1, PP1, and PP2A-B56, have all been shown to regulate both kinetochore-microtubule attachments and the spindle assembly checkpoint. Given that so many kinases and phosphatases converge onto two key mitotic processes, it is perhaps not surprising to learn that they are, quite literally, entangled in cross-talk. Inhibition of any one of these enzymes produces secondary effects on all the others, which results in a complicated picture that is very difficult to interpret...
2018: Frontiers in Cell and Developmental Biology
Hirokazu Nakatsumi, Takeru Oka, Tsunaki Higa, Michiko Shirane, Keiichi I Nakayama
Mammalian target of rapamycin complex 1 (mTORC1) kinase is a master regulator of the cellular response to nutrition-related signals such as insulin and amino acids. mTORC1 is activated on the lysosomal membrane and induces phosphorylation of a variety of downstream molecules. We previously showed that activated mTORC1 induces protein phosphatase 2A (PP2A)-mediated dephosphorylation of the transcription factor forkhead box K1 (FOXK1). The mechanism underlying the signal transduction from the cytoplasmic mTORC1 to the nuclear FOXK1 has remained unclear, however, we now show that a nuclear-cytoplasmic transport system is necessary for the mTORC1-FOXK1 signal transduction...
July 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Shuhei Enjoji, Ryotaro Yabe, Shunya Tsuji, Kazuhiro Yoshimura, Hideyoshi Kawasaki, Masashi Sakurai, Yusuke Sakai, Hiroko Takenouchi, Shigefumi Yoshino, Shoichi Hazama, Hiroaki Nagano, Hiroko Oshima, Masanobu Oshima, Michael P Vitek, Tetsuya Matsuura, Yoshitaka Hippo, Tatsuya Usui, Takashi Ohama, Koichi Sato
Gastric cancer is the fifth most common malignancy and the third leading cause of cancer-related deaths worldwide. Chemotherapies against gastric cancer often fail, with cancer recurrence due potentially to the persistence of cancer stem cells. This unique subpopulation of cells in tumors possesses the ability to self-renew and dedifferentiate. These cancer stem cells are critical for initiation, maintenance, metastasis, and relapse of cancers; however, the molecular mechanisms supporting cancer stemness remain largely unknown...
March 2018: Molecular Cancer Research: MCR
Edward L Evans, Jordan T Becker, Stephanie L Fricke, Kishan Patel, Nathan M Sherer
Cells derived from mice and other rodents exhibit profound blocks to HIV-1 virion production, reflecting species-specific incompatibilities between viral Tat and Rev proteins and essential host factors cyclin T1 (CCNT1) and exportin-1 (XPO1, also known as CRM1), respectively. To determine if mouse cell blocks other than CCNT1 and XPO1 affect HIV's postintegration stages, we studied HIV-1NL4-3 gene expression in mouse NIH 3T3 cells modified to constitutively express HIV-1-compatible versions of CCNT1 and XPO1 (3T3...
April 1, 2018: Journal of Virology
Thomas Kruse, Nadine Biedenkopf, Emil Peter Thrane Hertz, Erik Dietzel, Gertrud Stalmann, Blanca López-Méndez, Norman E Davey, Jakob Nilsson, Stephan Becker
Transcription of the Ebola virus genome depends on the viral transcription factor VP30 in its unphosphorylated form, but the underlying molecular mechanism of VP30 dephosphorylation is unknown. Here we show that the Ebola virus nucleoprotein (NP) recruits the host PP2A-B56 protein phosphatase through a B56-binding LxxIxE motif and that this motif is essential for VP30 dephosphorylation and viral transcription. The LxxIxE motif and the binding site of VP30 in NP are in close proximity, and both binding sites are required for the dephosphorylation of VP30...
January 4, 2018: Molecular Cell
Ziming Mao, Chunying Liu, Xuejing Lin, Bin Sun, Changqing Su
Protein phosphatase 2, regulatory subunit B (B56), alpha isoform (PPP2R5A) is one of the regulatory subunits of the protein phosphatase 2A (PP2A), which is a major member of protein serine/threonine phosphatases in cells. PPP2R5A can regulate the cellular location, substrate specification and protein phosphatase function of PP2A, through which PPP2R5A plays an important role in many cellular activities. It has been reported that PPP2R5A relates with many diseases including some kinds of cancers, but the related mechanisms have a lot remaining to be discovered or demonstrated...
February 1, 2018: Cancer Letters
Katharina Schleicher, Michael Porter, Sara Ten Have, Ramasubramanian Sundaramoorthy, Iain M Porter, Jason R Swedlow
Regulation of protein phosphatase activity by endogenous protein inhibitors is an important mechanism to control protein phosphorylation in cells. We recently identified Biorientation defective 1 (Bod1) as a small protein inhibitor of protein phosphatase 2A containing the B56 regulatory subunit (PP2A-B56). This phosphatase controls the amount of phosphorylation of several kinetochore proteins and thus the establishment of load-bearing chromosome-spindle attachments in time for accurate separation of sister chromatids in mitosis...
November 2017: Open Biology
C Lambrecht, L Libbrecht, X Sagaert, P Pauwels, Y Hoorne, J Crowther, J V Louis, W Sents, A Sablina, V Janssens
Protein Phosphatase 2A (PP2A) enzymes counteract diverse kinase-driven oncogenic pathways and their function is frequently impaired in cancer. PP2A inhibition is indispensable for full transformation of human cells, but whether loss of PP2A is sufficient for tumorigenesis in vivo has remained elusive. Here, we describe spontaneous tumor development in knockout mice for Ppp2r5d, encoding the PP2A regulatory B56δ subunit. Several primary tumors were observed, most commonly, hematologic malignancies and hepatocellular carcinomas (HCCs)...
January 25, 2018: Oncogene
Hila Shomin-Levi, Oded Yarden
COT1 is the founding member of the highly conserved nuclear Dbf2-related (NDR) Ser/Thr kinase family and plays a role in the regulation of polar growth and development in Neurospora crassa and other fungi. Changes in COT1 phosphorylation state have been shown to affect hyphal elongation, branching, and conidiation. The function of NDR protein kinases has been shown to be regulated by type 2A protein phosphatases (PP2As). PP2As are heterotrimers comprised of a catalytic and scaffolding protein along with an interchangeable regulatory subunit involved in determining substrate specificity...
2017: Frontiers in Microbiology
Giulia Vallardi, Marilia Henriques Cordeiro, Adrian Thomas Saurin
The KMN network (for KNL1, MIS12 and NDC80 complexes) is a hub for signalling at the outer kinetochore. It integrates the activities of two kinases (MPS1 and Aurora B) and two phosphatases (PP1 and PP2A-B56) to regulate kinetochore-microtubule attachments and the spindle assembly checkpoint (SAC). We will first discuss each of these enzymes separately, to describe how they are regulated at kinetochores and why this is important for their primary function in controlling either microtubule attachments or the SAC...
2017: Progress in Molecular and Subcellular Biology
Emil Peter Thrane Hertz, Jakob Nilsson
Protection of chromosome cohesion through Shugoshin-dependent recruitment of the PP2A-B56 phosphatase to the pericentromeric region has become a cornerstone of the chromosome segregation model in eukaryotes. Shugoshin is essential for meiotic chromosome segregation in all tested eukaryotes but only found to be essential for mitotic chromosome segregation in vertebrates. Nishiyama and colleagues have now found that the protein Dalmatian, an ortholog of the vertebrate cohesion regulator Sororin, performs the function of Shugoshin in Drosophila melanogaster by recruiting PP2A-B56 to the pericentromeric region supporting an unified model of mitotic chromosome segregation in the animal kingdom...
July 19, 2017: Cell Cycle
Emil Hertz, Thrane Hertz, Jakob Nilsson
No abstract text is available yet for this article.
July 19, 2017: Cell Cycle
Veena Theendakara, Dale E Bredesen, Rammohan V Rao
The apolipoprotein E ε4 allele is the single most important genetic risk factor associated with Alzheimer's disease (AD). Tau phosphorylation and hyperphosphorylation is an underlying feature of AD and is regulated by specific kinases and phosphatases. Among phosphatases, protein phosphatase 2A (PP2A) is the principal tau dephosphorylating enzyme in the brain. Several abnormalities of PP2A have been reported in AD, including among others decreased protein levels of PP2A, decreased mRNA and protein levels of the catalytic subunit PP2AC and variable regulatory B subunits and reduced methylation of the catalytic subunit, all of which results in disruption of the PP2A phosphatase activity...
September 2017: Molecular and Cellular Neurosciences
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