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dictyNews Volume 41 Number 21
dictyNews
Electronic Edition
Volume 41, number 21
October 2, 2015
Please submit abstracts of your papers as soon as they have been
accepted for publication by sending them to dicty@northwestern.edu
or by using the form at
http://dictybase.org/db/cgi-bin/dictyBase/abstract_submit.
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Abstracts
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A Derivative of Differentiation-inducing Factor-3 Inhibits
PAK1 Activity and Breast Cancer Cell Proliferation
Peter Oladimeji, Yuzuru Kubohara, Haruhisa Kikuchi,
Yoshiteru Oshima, Courtney Rusch, Rebekah Skerl, &
Maria Diakonova #
# Corresponding Author. The Department of Biological
Sciences, University of Toledo, Ohio, USA 43606-3390
Accepted for publication in Int. J. Cancer Clin. Res.
Differentiation-inducing factors 1-3 (DIFs 1-3), chlorinated
alkylphenones identified in the cellular slime mold
Dictyostelium discoideum, are considered anti-tumor agents
because they inhibit proliferation of a variety of mammalian
tumor cells in vitro. Although the anti-proliferative effects
of DIF-1 and DIF-3 are well-documented, the precise molecular
mechanisms underlying the actions of DIFs have not been fully
elucidated. In this study, we examined the effects of DIFs and
their derivatives on PAK1, a key serine-threonine kinase, which
is activated by multiple ligands and regulates cell proliferation.
We examined the effect of DIF derivatives on PAK1 kinase activity
in cells. We also examined the effect of DIF-3(+1) derivative on
PAK1 kinase activity in vitro, cyclin D1 promoter activity and
breast cancer cell proliferation. It was found that some
derivatives strongly inhibited PAK1 kinase activity in human
breast cancer MCF-7 cells stably overexpressing PAK1. Among
the derivatives, DIF-3(+1) was most potent, which directly
inhibited kinase activity of recombinant purified PAK1 in an
in vitro kinase assay. Furthermore, DIF-3(+1) strongly inhibited
both cyclin D1 promoter activity and proliferation of MCF-7 and
T47D breast cancer cells stably overexpressing PAK1 in response
to prolactin, estrogen, epidermal growth factor and heregulin.
In the present study we propose PAK1 as DIF-3(+1) target mediating
its anti-proliferative effect.
Submitted by Yuzuru Kubohara [ykuboha@juntendo.ac.jp]
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Dynamic modulation of Dnmt2-dependent tRNA methylation by the
micronutrient queuine
Martin Müller1, Mark Hartmann2, Isabelle Schuster3, Sebastian Bender2,
Kathrin L. Thüring4, Mark Helm4, Jon R. Katze5, Wolfgang Nellen3,
Frank Lyko2 and Ann E. Ehrenhofer-Murray1*
1 Institut für Biologie, Humboldt-Universität zu Berlin, 10115 Berlin,
Germany
2 Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research
Center, 69120 Heidelberg, Germany
3 Abteilung für Genetik, Universität Kassel, 34132 Kassel, Germany
4 Institut für Pharmakologie und Biochemie, Johannes
Gutenberg-Universität Mainz, 55099 Mainz, Germany
5 Department of Microbiology, Immunology and Biochemistry, University
of Tennessee Health Science Center, Memphis, TN 38163, USA
accepted: Nucleic Acids Res.
ABSTRACT
Dnmt2 enzymes are cytosine-5 methyltransferases that methylate C38 of
several tRNAs. We report here that the activities of two Dnmt2 homologs,
Pmt1 from Schizosaccharomyces pombe and DnmA from Dictyostelium
discoideum, are strongly stimulated by prior queuosine (Q) modification
of the substrate tRNA. In vivo tRNA methylation levels were stimulated
by growth of cells in queuine-containing medium; in vitro Pmt1 activity
was enhanced on Q-containing RNA; and queuine-stimulated in vivo
methylation was abrogated by the absence of the enzyme that inserts
queuine into tRNA, eukaryotic tRNA-guanine transglycosylase. Global
analysis of tRNA methylation in S. pombe showed a striking selectivity
of Pmt1 for tRNAAsp methylation, which distinguishes Pmt1 from other
Dnmt2 homologs. The present analysis also revealed a novel Pmt1- and
Q-independent tRNA methylation site in S. pombe, C34 of tRNAPro.
Notably, queuine is a micronutrient that is scavenged by higher
eukaryotes from the diet and gut microflora. This work therefore
reveals an unanticipated route by which the environment can modulate
tRNA modification in an organism.
Submitted by Wolfgang Nellen [nellen@uni-kassel.de]
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A resilient formin-derived cortical actin meshwork in the rear drives
actomyosin-based motility in 2D confinement
Nagendran Ramalingam1,2,*, Christof Franke 3,*, Evelin Jaschinski 4,
Moritz Winterhoff 3, Yao Lu 5, Stefan Brühmann 3, Alexander Junemann 3,
Helena Meier 3, Angelika A. Noegel 6, Igor Weber 7, Hongxia Zhao 5,
Rudolf Merkel 4, Michael Schleicher 1, and Jan Faix 3
* These authors contributed equally to this work
1 Anatomy III/Cell Biology, BioMedCenter, Ludwig-Maximilians-University,
Grosshaderner Str. 9, Planegg-Martinsried, Germany;
2 present address: Department of Neurology, Columbia University,
650 West 168th Street, New York, NY 10032, USA;
3 Institute for Biophysical Chemistry, Hannover Medical School,
Carl-Neuberg-Str. 1, 30625 Hannover, Germany;
4 Instituteof Complex Systems, ICS-7: Biomechanics, Forschungszentrum
Jülich GmbH, 52425 Jülich, Germany;
5 Institute of Biotechnology, PO Box 56, University of Helsinki, Helsinki
00014, Finland;
6 Center for Biochemistry, Medical Faculty, University of Cologne,
50931 Köln, Germany;
7 Division of Molecular Biology, Ruder Boškovic; Institute,
Bijenicka 54, 10000 Zagreb, Croatia.
Nature Communications, in press
Cell migration is driven by the establishment of disparity between the
cortical properties ofthe softer front and the more rigid rear allowing
front extension and actomyosin-based rearcontraction. However, how the
cortical actin meshwork in the rear is generated remains elusive. Here
we identify the mDia1-like formin A (ForA) from Dictyostelium discoideum
that generates a subset of filaments as the basis of a resilient cortical
actin sheath in the rear. Mechanical resistance of this actin compartment
is accomplished by actin crosslinkers and IQGAP-related proteins, and is
mandatory to withstand the increased contractile forces in response to
mechanical stress by impeding unproductive blebbing in the rear, allowing
efficient cell migration in two-dimensional-confined environments.
Consistently, ForA supresses the formation of lateral protrusions,
rapidly relocalizes to new prospective ends in repolarizing cells and is
required for cortical integrity. Finally, we show that ForA utilizes the
phosphoinositide gradients in polarized cells for subcellular targeting.
Submitted by Jan Faix [faix.jan@mh-hannover.de]
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[End dictyNews, volume 41, number 21]
