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dictyNews Volume 27 Number 11
dictyNews
Electronic Edition
Volume 27, number 11
October 6, 2006
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.
Back issues of dictyNews, the Dicty Reference database and other
useful information is available at dictyBase - http://dictybase.org.
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Abstracts
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Molecular phylogeny and evolution of morphology in the social amoebas
1Pauline Schaap, 2Thomas Winckler, 3Michaela Nelson, 1Elisa Alvarez-Curto,
3Barrie Elgie, 4Hiromitsu Hagiwara, 5James Cavender, 1Alicia Milano-Curto,
1Daniel E. Rozen, 6Theodor Dingermann, 7 Rupert Mutzel and
3Sandra L. Baldauf*
Science, in press
The social amoebas (Dictyostelia) display conditional multicellularity in a
wide variety of forms. Despite widespread interest in Dictyostelium
discoideum as a model system, there is almost no molecular data from the
rest of the group. We have constructed the first molecular phylogeny of the
Dictyostelia with parallel small subunit ribosomal RNA and alpha-tubulin
datasets and find that dictyostelid taxonomy requires complete revision. A
mapping of characters onto the phylogeny shows that the dominant trend in
dictyostelid evolution is increased size and cell-type specialization of
fruiting structures, but not architectural complexity. This major taxon is
now uniquely well suited to study molecular changes underlying phenotypic
innovation.
Submitted by: Pauline Schaap [p.schaap@dundee.ac.uk]
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Pharmacological profiling of the Dictyostelium adenylyl cyclases ACA, ACB
and ACG.
Elisa Alvarez-Curto, Karin E. Weening and Pauline Schaap
Biochemical Journal, in press
Intracellular and secreted cAMP play crucial roles in controlling cell
movement and gene regulation throughout development of the social amoeba
Dictyostelium discoideum. cAMP is produced by three structurally distinct
adenylyl cyclases, ACA, ACG and ACB which have distinctive but overlapping
patterns of expression and, as concluded from gene disruption studies,
seemingly overlapping functions. In addition to gene disruption, acute
pharmacological abrogation of protein activity can be a powerful tool to
identify its role in the biology of the organism. We analysed the effects
of a range of compounds on the activity of ACA, ACB and ACG to identify
enzyme-specific modulators. Caffeine, which was previously used to
specifically block ACA function, also inhibited cAMP accumulation by ACB
and ACG. 2'3'-O-methyl isopropylidene adenosine (IPA) specifically inhibits
ACA when measured in intact cells, without affecting ACB or ACG. All three
enzymes are inhibited by the P-site inhibitor 2'5'dideoxyadenosine (DDA)
when assayed in cell lysates, but not in intact cells. Tyrphostin A25 and
SQ22536 proved to be effective and specific inhibitors for ACG and ACA
respectively. Both compounds acted directly on enzyme activity assayed in
cell lysates, but only SQ22536 was also a specific inhibitor when added
to intact cells.
Submitted by: Pauline Schaap [p.schaap@dundee.ac.uk]
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Correction of the abstract that appeared in the dictyNews, v27, #7:
Anti-leukemic activities of Dictyostelium secondary metabolites: A novel
aromatic metabolite, 4-methyl-5-n-pentylbenzene-1,3-diol, isolated from
Dictyostelium mucoroides suppresses cell growth in human leukemia K562 and
HL-60 cells.
Haruhisa Kikuchi, Yoshiteru Oshima, Aya Ichimura, Naomi Gokan, Aiko
Hasegawa, Kohei Hosaka, Yuzuru Kubohara
Tohoku University & Gunma University, Japan.
Life Sciences, In press
It has previously been shown that DIF-1, a differentiation-inducing factor
of the cellular slime mold Dictyostelium discoideum, possesses antitumor
activities in mammalian tumor cells and that neuronal differentiation of
PC12 cells can be induced with furanodictines (FDs), aminosugar analogs
found in D. discoideum, or dictyoglucosamines (DGs), N-acetyl glucosamine
derivatives (DG-A from D. purpureum and DG-B from D. discoideum). Thus,
cellular slime molds are attractive natural resources that may provide
valuable lead compounds to be utilized in the field of pharmacology and
medicine. In this study, we have isolated a novel aromatic compound,
4-methyl-5-n-pentylbenzene-1,3-diol (MPBD), from fruiting bodies of the
cellular slime mold D. mucoroides and assessed the in vitro
antiproliferative activities of MPBD, FDs, and DGs in human leukemia
K562 and HL-60 cells. MPBD at 20-80 microM dose-dependently suppressed
cell growth in both K562 and HL-60 cells. While FDs at 10-80 microM did
not affect cell growth, DGs at 10-40 microM dose-dependently suppressed
cell growth in the cells. Although we failed to find the roles of FDs
and DGs in the original organisms, MPBD at 5-20 microM was found to promote
stalk cell formation in D. discoideum. The present results indicate that
MPBD, DGs or their derivatives may have therapeutic potential in the
treatment of cancer and confirm our expectations regarding cellular slime
molds as drug resources.
Submitted by: Yuzuru Kubohara [kubohara@showa.gunma-u.ac.jp]
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[End dictyNews, volume 27, number 11]