9607
2013
eng
article
1
--
--
--
The Budding Yeast Cdc48Shp1 Complex Promotes Cell Cycle Progression by Positive Regulation of Protein Phosphatase 1 (Glc7)
The conserved, ubiquitin-selective AAA ATPase Cdc48 regulates numerous cellular processes including protein quality control, DNA repair and the cell cycle. Cdc48 function is tightly controlled by a multitude of cofactors mediating substrate specificity and processing. The UBX domain protein Shp1 is a bona fide substrate-recruiting cofactor of Cdc48 in the budding yeast S. cerevisiae. Even though Shp1 has been proposed to be a positive regulator of Glc7, the catalytic subunit of protein phosphatase 1 in S. cerevisiae, its cellular functions in complex with Cdc48 remain largely unknown. Here we show that deletion of the SHP1 gene results in severe growth defects and a cell cycle delay at the metaphase to anaphase transition caused by reduced Glc7 activity. Using an engineered Cdc48 binding-deficient variant of Shp1, we establish the Cdc48Shp1 complex as a critical regulator of mitotic Glc7 activity. We demonstrate that shp1 mutants possess a perturbed balance of Glc7 phosphatase and Ipl1 (Aurora B) kinase activities and show that hyper-phosphorylation of the kinetochore protein Dam1, a key mitotic substrate of Glc7 and Ipl1, is a critical defect in shp1. We also show for the first time a physical interaction between Glc7 and Shp1 in vivo. Whereas loss of Shp1 does not significantly affect Glc7 protein levels or localization, it causes reduced binding of the activator protein Glc8 to Glc7. Our data suggest that the Cdc48Shp1 complex controls Glc7 activity by regulating its interaction with Glc8 and possibly further regulatory subunits.
PLoS One
10.1371/journal.pone.0056486
urn:nbn:de:bvb:20-opus-96073
In: PLoS One (2013) 8: 2, doi:10.1371/journal.pone.0056486
Alexander Buchberger
Stephanie Böhm
eng
uncontrolled
alleles
eng
uncontrolled
cell cycle
eng
uncontrolled
immunoprecipitation
eng
uncontrolled
phosphatases
eng
uncontrolled
genetic interactions
Chemie und zugeordnete Wissenschaften
open_access
Lehrstuhl für Biochemie
Förderzeitraum 2013
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/9607/Buchberger_journal.pone.0056486.pdf
21817
eng
10
12
article
1
--
2020-10-14
--
Merkel Cell Polyomavirus Large T Antigen is Dispensable in G2 and M-Phase to Promote Proliferation of Merkel Cell Carcinoma Cells
Merkel cell carcinoma (MCC) is an aggressive skin cancer frequently caused by the Merkel cell polyomavirus (MCPyV), and proliferation of MCPyV-positive MCC tumor cells depends on the expression of a virus-encoded truncated Large T antigen (LT) oncoprotein. Here, we asked in which phases of the cell cycle LT activity is required for MCC cell proliferation. Hence, we generated fusion-proteins of MCPyV-LT and parts of geminin (GMMN) or chromatin licensing and DNA replication factor1 (CDT1). This allowed us to ectopically express an LT, which is degraded either in the G1 or G2 phase of the cell cycle, respectively, in MCC cells with inducible T antigen knockdown. We demonstrate that LT expressed only in G1 is capable of rescuing LT knockdown-induced growth suppression while LT expressed in S and G2/M phases fails to support proliferation of MCC cells. These results suggest that the crucial function of LT, which has been demonstrated to be inactivation of the cellular Retinoblastoma protein 1 (RB1) is only required to initiate S phase entry.
Viruses
1999-4915
10.3390/v12101162
urn:nbn:de:bvb:20-opus-218171
2020-12-07T10:34:48+00:00
sword
swordwue
attachment; filename=deposit.zip
4ffaaab772f793b24889c3e527e45e74
Viruses 2020, 12(10), 1162; https://doi.org/10.3390/v12101162
true
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Roland Houben
Marlies Ebert
Sonja Hesbacher
Thibault Kervarrec
David Schrama
eng
uncontrolled
Merkel cell polyomavirus
eng
uncontrolled
large T antigen
eng
uncontrolled
cell cycle
eng
uncontrolled
Merkel cell carcinoma
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
Import
Förderzeitraum 2020
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/21817/viruses-12-01162.pdf
9692
2013
eng
article
1
--
--
--
LIN9, a Subunit of the DREAM Complex, Regulates Mitotic Gene Expression and Proliferation of Embryonic Stem Cells
The DREAM complex plays an important role in regulation of gene expression during the cell cycle. We have previously shown that the DREAM subunit LIN9 is required for early embryonic development and for the maintenance of the inner cell mass in vitro. In this study we examined the effect of knocking down LIN9 on ESCs. We demonstrate that depletion of LIN9 alters the cell cycle distribution of ESCs and results in an accumulation of cells in G2 and M and in an increase of polyploid cells. Genome-wide expression studies showed that the depletion of LIN9 results in downregulation of mitotic genes and in upregulation of differentiation-specific genes. ChIP-on chip experiments showed that mitotic genes are direct targets of LIN9 while lineage specific markers are regulated indirectly. Importantly, depletion of LIN9 does not alter the expression of pluripotency markers SOX2, OCT4 and Nanog and LIN9 depleted ESCs retain alkaline phosphatase activity. We conclude that LIN9 is essential for proliferation and genome stability of ESCs by activating genes with important functions in mitosis and cytokinesis.
PLoS ONE
10.1371/journal.pone.0062882
urn:nbn:de:bvb:20-opus-96922
In: PLoS One (2013) 8: 5, doi:10.1371/journal.pone.0062882
Stefan Gaubatz
Jasmina Esterlechner
Nina Reichert
Fabian Iltzsche
Michael Krause
Florian Finkernagel
eng
uncontrolled
cell cycle
eng
uncontrolled
cell division
eng
uncontrolled
cell differentation
eng
uncontrolled
DNA-binding proteins
eng
uncontrolled
gene expression
eng
uncontrolled
gene regulation
eng
uncontrolled
gene targeting
eng
uncontrolled
microarrays
eng
uncontrolled
pluripotency
Biowissenschaften; Biologie
open_access
Theodor-Boveri-Institut für Biowissenschaften
Förderzeitraum 2013
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/9692/Gaubatz_journal.pone.0062882.pdf
5715
1991
eng
article
1
2012-03-20
--
--
Interleukin 4 drives phytohemagglutinin-activated T cells through several cell cycles: no synergism between interleukin 2 and interleukin 4
Cell kinetic studies of T cells stimulated with the interleukin 2 (11-2), D-4, or both lymphokines were performed with conventional [3H] thymidine incorporation and with the bivariate BrdU/Hoechst technique. 11-2 and 11-4 are able to drive phytohemagglutininactivated T cells through more than one cell cycle. Neither synergistic nor inhibitory efl'ect on T -cell proliferationwas seen for the stimulation with both 11-2 and 11-4 as compared with the effect ofll-2 alone. The quantitative data ofthe cell cycle distribution ofphytohemagglutininactivated T cells suggestthat the population ofll-4-responsive cells is at least an overlapping population, if not a real subset of the ·population of the 11-2-responsive cells.
urn:nbn:de:bvb:20-opus-62491
6249
In: Cytokine (1991 Nov) 6, 3, 593-597.
Deutsches Urheberrecht
T. Lehrnbecher
H. Merz
Walter Sebald
M. Poot
deu
swd
Biochemie
eng
uncontrolled
BrdU-Hoechst
eng
uncontrolled
cell cycle
eng
uncontrolled
flow cytometry
eng
uncontrolled
interleukin 2
eng
uncontrolled
interleukin 4
Biowissenschaften; Biologie
open_access
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/5715/Sebald14.pdf
14043
2011
eng
1-16
7
2
article
1
2016-11-16
--
--
Helicobacter pylori interferes with an embryonic stem cell micro RNA cluster to block cell cycle progression
Background
MicroRNAs, post-transcriptional regulators of eukaryotic gene expression, are implicated in host defense against pathogens. Viruses and bacteria have evolved strategies that suppress microRNA functions, resulting in a sustainable infection. In this work we report that Helicobacter pylori, a human stomach-colonizing bacterium responsible for severe gastric inflammatory diseases and gastric cancers, downregulates an embryonic stem cell microRNA cluster in proliferating gastric epithelial cells to achieve cell cycle arrest.
Results
Using a deep sequencing approach in the AGS cell line, a widely used cell culture model to recapitulate early events of H. pylori infection of gastric mucosa, we reveal that hsa-miR-372 is the most abundant microRNA expressed in this cell line, where, together with hsa-miR-373, it promotes cell proliferation by silencing large tumor suppressor homolog 2 (LATS2) gene expression. Shortly after H. pylori infection, miR-372 and miR-373 synthesis is highly inhibited, leading to the post-transcriptional release of LATS2 expression and thus, to a cell cycle arrest at the G1/S transition. This downregulation of a specific cell-cycle-regulating microRNA is dependent on the translocation of the bacterial effector CagA into the host cells, a mechanism highly associated with the development of severe atrophic gastritis and intestinal-type gastric carcinoma.
Conclusions
These data constitute a novel example of host-pathogen interplay involving microRNAs, and unveil the couple LATS2/miR-372 and miR-373 as an unexpected mechanism in infection-induced cell cycle arrest in proliferating gastric cells, which may be relevant in inhibition of gastric epithelium renewal, a major host defense mechanism against bacterial infections.
Silence : a Journal of RNA regulation
10.1186/1758-907X-2-7
urn:nbn:de:bvb:20-opus-140438
Silence 2011 2:7.
Cédric Belair
Jessica Baud
Sandrine Chabas
Cynthia M Sharma
Jörg Vogel
Cathy Staedel
Fabien Darfeuille
eng
uncontrolled
MicroRNAs
eng
uncontrolled
cell cycle
eng
uncontrolled
Helicobacter pylori
eng
uncontrolled
gastric cancer
Krankheiten
open_access
Institut für Molekulare Infektionsbiologie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/14043/064_Belair_Silence.pdf
23057
2020
eng
9660-9680
17
48
article
1
2021-03-11
--
--
Genome maintenance functions of a putative Trypanosoma brucei translesion DNA polymerase include telomere association and a role in antigenic variation
Maintenance of genome integrity is critical to guarantee transfer of an intact genome from parent to off-spring during cell division. DNA polymerases (Pols) provide roles in both replication of the genome and the repair of a wide range of lesions. Amongst replicative DNA Pols, translesion DNA Pols play a particular role: replication to bypass DNA damage. All cells express a range of translesion Pols, but little work has examined their function in parasites, including whether the enzymes might contribute to host-parasite interactions. Here, we describe a dual function of one putative translesion Pol in African trypanosomes, which we now name TbPolIE. Previously, we demonstrated that TbPolIE is associated with telomeric sequences and here we show that RNAi-mediated depletion of TbPolIE transcripts results in slowed growth, altered DNA content, changes in cell morphology, and increased sensitivity to DNA damaging agents. We also show that TbPolIE displays pronounced localization at the nuclear periphery, and that its depletion leads to chromosome segregation defects and increased levels of endogenous DNA damage. Finally, we demonstrate that TbPolIE depletion leads to deregulation of telomeric variant surface glycoprotein genes, linking the function of this putative translesion DNA polymerase to host immune evasion by antigenic variation.
Nucleic Acids Research
10.1093/nar/gkaa686
urn:nbn:de:bvb:20-opus-230579
publish
Nucleic Acids Research, 2020, 48(17), 9660–9680. doi: 10.1093/nar/gkaa686
true
true
CC BY-NC: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell 4.0 International
Andrea Zurita Leal
Marie Schwebs
Emma Briggs
Nadine Weisert
Helena Reis
Leondro Lemgruber
Katarina Luko
Jonathan Wilkes
Falk Butter
Richard McCulloch
Christian J. Janzen
eng
uncontrolled
cross-link repair
eng
uncontrolled
cell cycle
eng
uncontrolled
gene expression
eng
uncontrolled
low fidelity
eng
uncontrolled
replication
eng
uncontrolled
bypass
eng
uncontrolled
theta
eng
uncontrolled
reveals
eng
uncontrolled
binding
Biowissenschaften; Biologie
open_access
Theodor-Boveri-Institut für Biowissenschaften
Förderzeitraum 2020
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/23057/gkaa686.pdf
17185
2017
eng
11160-11172
7
8
article
1
2018-11-15
--
--
Central spindle proteins and mitotic kinesins are direct transcriptional targets of MuvB, B-MYB and FOXM1 in breast cancer cell lines and are potential targets for therapy
The MuvB multiprotein complex, together with B-MYB and FOXM1 (MMB-FOXM1), plays an essential role in cell cycle progression by regulating the transcription of genes required for mitosis and cytokinesis. In many tumors, B-MYB and FOXM1 are overexpressed as part of the proliferation signature. However, the transcriptional targets that are important for oncogenesis have not been identified. Given that mitotic kinesins are highly expressed in cancer cells and that selected kinesins have been reported as target genes of MMB-FOXM1, we sought to determine which mitotic kinesins are directly regulated by MMB-FOXM1. We demonstrate that six mitotic kinesins and two microtubule-associated non-motor proteins (MAPs) CEP55 and PRC1 are direct transcriptional targets of MuvB, B-MYB and FOXM1 in breast cancer cells.
Suppression of KIF23 and PRC1 strongly suppressed proliferation of MDA-MB-231 cells. The set of MMB-FOXM1 regulated kinesins genes and 4 additional kinesins which we referred to as the mitotic kinesin signature (MKS) is linked to poor outcome in breast cancer patients. Thus, mitotic kinesins could be used as prognostic biomarker and could be potential therapeutic targets for the treatment of breast cancer.
Oncotarget
10.18632/oncotarget.14466
28061449
urn:nbn:de:bvb:20-opus-171851
Oncotarget (2017) 8:7, pp. 11160-11172. https://doi.org/10.18632/oncotarget.14466
true
true
Patrick Wolter
Steffen Hanselmann
Grit Pattschull
Eva Schruf
Stefan Gaubatz
eng
uncontrolled
breast cancer
eng
uncontrolled
kinesin
eng
uncontrolled
cell cycle
eng
uncontrolled
cytokinesis
Medizin und Gesundheit
open_access
Theodor-Boveri-Institut für Biowissenschaften
Medizinische Klinik und Poliklinik II
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/17185/Wolter_14466-215090-2-PB.pdf