Bastians, Holger

[["dc.bibliographiccitation.firstpage","401"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Clinical Cancer Research"],["dc.bibliographiccitation.lastpage","405"],["dc.bibliographiccitation.volume","17"],["dc.contributor.author","Stolz, Ailine"],["dc.contributor.author","Ertych, Norman"],["dc.contributor.author","Bastians, Holger"],["dc.date.accessioned","2018-11-07T08:59:45Z"],["dc.date.available","2018-11-07T08:59:45Z"],["dc.date.issued","2011"],["dc.description.abstract","CHK2 is a multiorgan tumor susceptibility gene that encodes for a serine/threonine protein kinase involved in the response to cellular DNA damage. After ATM-mediated phosphorylation, the activated Chk2 kinase can act as a signal transducer and phosphorylate a variety of substrates, including the Cdc25 phosphatases, p53, PML, E2F-1, and Brca1, which has been associated with halting the cell cycle, the initiation of DNA repair, and the induction of apoptosis after DNA damage. In addition, recent work has revealed another, DNA-damage-independent function of Chk2 during mitosis that is required for proper mitotic spindle assembly and maintenance of chromosomal stability. This novel role involves a mitotic phosphorylation of the tumor suppressor Brca1 by the Chk2 kinase. On the basis of its role during DNA damage response, Chk2 has been suggested as an anticancer therapy target, but given its recently discovered new function and its role as a tumor suppressor, it is questionable whether inhibition of Chk2 is indeed beneficial for anticancer treatment. However, investigators may be able to exploit the loss of CHK2 in human tumors to develop novel therapies based on synthetic lethal interactions. Clin Cancer Res; 17(3); 401-5. (C) 2010 AACR."],["dc.identifier.doi","10.1158/1078-0432.CCR-10-1215"],["dc.identifier.isi","000286873400003"],["dc.identifier.pmid","21088254"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/23979"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Cancer Research"],["dc.relation.issn","1078-0432"],["dc.title","Tumor Suppressor CHK2: Regulator of DNA Damage Response and Mediator of Chromosomal Stability"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","e960768"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Molecular & Cellular Oncology"],["dc.bibliographiccitation.volume","2"],["dc.contributor.author","Stolz, Ailine"],["dc.contributor.author","Ertych, Norman"],["dc.contributor.author","Bastians, Holger"],["dc.date.accessioned","2021-06-01T10:48:54Z"],["dc.date.available","2021-06-01T10:48:54Z"],["dc.date.issued","2014"],["dc.identifier.doi","10.4161/23723548.2014.960768"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86093"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation.eissn","2372-3556"],["dc.title","Microtubule plus tips: A dynamic route to chromosomal instability"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","490"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","EMBO Reports"],["dc.bibliographiccitation.lastpage","499"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Stolz, Ailine"],["dc.contributor.author","Neufeld, Kim"],["dc.contributor.author","Ertych, Norman"],["dc.contributor.author","Bastians, Holger"],["dc.date.accessioned","2021-06-01T10:48:25Z"],["dc.date.available","2021-06-01T10:48:25Z"],["dc.date.issued","2015"],["dc.description.abstract","Wnt signaling stimulates cell proliferation by promoting the G1/S transition of the cell cycle through beta-catenin/TCF4-mediated gene transcription. However, Wnt signaling peaks in mitosis and contributes to the stabilization of proteins other than beta-catenin, a pathway recently introduced as Wnt-dependent stabilization of proteins (Wnt/STOP). Here, we show that Wnt/STOP regulated by basal Wnt signaling during a normal cell cycle is required for proper spindle microtubule assembly and for faithful chromosome segregation during mitosis. Consequently, inhibition of basal Wnt signaling results in increased microtubule assembly rates, abnormal mitotic spindle formation and the induction of aneuploidy in human somatic cells."],["dc.identifier.doi","10.15252/embr.201439410"],["dc.identifier.isi","352167500012"],["dc.identifier.pmid","25656539"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85930"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.eissn","1469-3178"],["dc.relation.issn","1469-221X"],["dc.title","Wnt‐mediated protein stabilization ensures proper mitotic microtubule assembly and chromosome segregation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1817"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA"],["dc.bibliographiccitation.lastpage","1822"],["dc.bibliographiccitation.volume","113"],["dc.contributor.author","Ertych, Norman"],["dc.contributor.author","Stolz, Ailine"],["dc.contributor.author","Valerius, Oliver"],["dc.contributor.author","Braus, Gerhard H."],["dc.contributor.author","Bastians, Holger"],["dc.date.accessioned","2018-11-07T10:18:11Z"],["dc.date.available","2018-11-07T10:18:11Z"],["dc.date.issued","2016"],["dc.description.abstract","BRCA1 (breast cancer type 1 susceptibility protein) is a multifunctional tumor suppressor involved in DNA damage response, DNA repair, chromatin regulation, and mitotic chromosome segregation. Although the nuclear functions of BRCA1 have been investigated in detail, its role during mitosis is little understood. It is clear, however, that loss of BRCA1 in human cancer cells leads to chromosomal instability (CIN), which is defined as a perpetual gain or loss of whole chromosomes during mitosis. Moreover, our recent work has revealed that the mitotic function of BRCA1 depends on its phosphorylation by the tumor-suppressor kinase Chk2 (checkpoint kinase 2) and that this regulation is required to ensure normal microtubule plus end assembly rates within mitotic spindles. Intriguingly, loss of the positive regulation of BRCA1 leads to increased oncogenic Aurora-A activity, which acts as a mediator for abnormal mitotic microtubule assembly resulting in chromosome missegregation and CIN. However, how the CHK2-BRCA1 tumor suppressor axis restrains oncogenic Aurora-A during mitosis to ensure karyotype stability remained an open question. Here we uncover a dual molecular mechanism by which the CHK2-BRCA1 axis restrains oncogenic Aurora-A activity during mitosis and identify BRCA1 itself as a target for Aurora-A relevant for CIN. In fact, Chk2-mediated phosphorylation of BRCA1 is required to recruit the PP6C-SAPS3 phosphatase, which acts as a T-loop phosphatase inhibiting Aurora-A bound to BRCA1. Consequently, loss of CHK2 or PP6C-SAPS3 promotes Aurora-A activity associated with BRCA1 in mitosis. Aurora-A, in turn, then phosphorylates BRCA1 itself, thereby inhibiting the mitotic function of BRCA1 and promoting mitotic microtubule assembly, chromosome missegregation, and CIN."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft (DFG); DFG [KFO179]"],["dc.identifier.doi","10.1073/pnas.1525129113"],["dc.identifier.isi","000370220000047"],["dc.identifier.pmid","26831064"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41385"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Natl Acad Sciences"],["dc.relation.issn","0027-8424"],["dc.title","CHK2-BRCA1 tumor-suppressor axis restrains oncogenic Aurora-A kinase to ensure proper mitotic microtubule assembly"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","492"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Nature Cell Biology"],["dc.bibliographiccitation.lastpage","499"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Stolz, Ailine"],["dc.contributor.author","Ertych, Norman"],["dc.contributor.author","Kienitz, Anne"],["dc.contributor.author","Vogel, Celia"],["dc.contributor.author","Schneider, Verena"],["dc.contributor.author","Fritz, Barbara"],["dc.contributor.author","Jacob, Ralf"],["dc.contributor.author","Dittmar, Gunnar"],["dc.contributor.author","Weichert, Wilko"],["dc.contributor.author","Petersen, Iver"],["dc.contributor.author","Bastians, Holger"],["dc.date.accessioned","2019-07-09T11:52:59Z"],["dc.date.available","2019-07-09T11:52:59Z"],["dc.date.issued","2010"],["dc.description.abstract","Chromosomal instability (CIN) is a major hallmark of human cancer and might contribute to tumorigenesis1. Genes required for the normal progression of mitosis represent potential CIN genes and, as such, are important tumour suppressors. The Chk2 kinase and its downstream targets p53 and Brca1 are tumour suppressors that have been functionally linked to the DNA damage response pathway2. Here, we report a function of Chk2, independent of p53 and DNA damage, that is required for proper progression of mitosis, and for the maintenance of chromosomal stability in human somatic cells. Depletion of Chk2 or abrogation of its kinase activity causes abnormal mitotic spindle assembly associated with a delay in mitosis, which promotes the generation of lagging chromosomes, chromosome missegregation and CIN, while still allowing survival and growth. Furthermore, we have identified Brca1 as a mitotic target of the Chk2 kinase in the absence of DNA damage. Accordingly, loss of BRCA1 or its Chk2-mediated phosphorylation leads to spindle formation defects and CIN. Thus, the CHK2–BRCA1 tumour suppressor pathway is required for chromosomal stability, which might contribute to their tumour suppressor function."],["dc.identifier.doi","10.1038/ncb2051"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6282"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60314"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","The CHK2–BRCA1 tumour suppressor pathway ensures chromosomal stability in human somatic cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","827"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Cell Cycle"],["dc.bibliographiccitation.lastpage","837"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Stolz, Ailine"],["dc.contributor.author","Ertych, Norman"],["dc.contributor.author","Bastians, Holger"],["dc.date.accessioned","2018-11-07T09:59:37Z"],["dc.date.available","2018-11-07T09:59:37Z"],["dc.date.issued","2015"],["dc.description.abstract","Proper regulation of microtubule dynamics during mitosis is essential for faithful chromosome segregation. In fact, recently we discovered increased microtubule plus end assembly rates that are frequently observed in human cancer cells as an important mechanism leading to whole chromosome missegregation and chromosomal instability (CIN). However, the genetic alterations responsible for increased microtubule polymerization rates in cancer cells remain largely unknown. The identification of such lesions is hampered by the fact that determining dynamic parameters of microtubules usually involves analyses of living cells, which is technically difficult to perform in large-scale screening settings. Therefore, we sought to identify alternative options to systematically identify regulators of microtubule plus end polymerization. Here, we introduce a simple and robust phenotypic screening assay that is based on the analyses of monopolar mitotic spindle structures that are induced upon inhibition of the mitotic kinesin Eg5/KIF11. We show that increased microtubule polymerization causes highly asymmetric monoasters in the presence of Eg5/KIF11 inhibition and this phenotype can be reliably assessed in living as well as in fixed cells. Using this assay we performed a siRNA screen, in which we identify several microtubule plus end binding proteins as well as centrosomal and cortex associated proteins as important regulators of microtubule plus end assembly. Interestingly, we demonstrate that a subgroup of these regulators function in the regulation of spindle orientation through their role in dampening microtubule plus end polymerization."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft [KFO179]; DFG"],["dc.identifier.doi","10.1080/15384101.2014.1000693"],["dc.identifier.isi","000351598200014"],["dc.identifier.pmid","25590964"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37637"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Taylor & Francis Inc"],["dc.relation.issn","1551-4005"],["dc.relation.issn","1538-4101"],["dc.title","A phenotypic screen identifies microtubule plus end assembly regulators that can function in mitotic spindle orientation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2566"],["dc.bibliographiccitation.issue","16"],["dc.bibliographiccitation.journal","Cell Cycle"],["dc.bibliographiccitation.lastpage","2570"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Stolz, Ailine"],["dc.contributor.author","Bastians, Holger"],["dc.date.accessioned","2018-11-07T09:53:14Z"],["dc.date.available","2018-11-07T09:53:14Z"],["dc.date.issued","2015"],["dc.description.abstract","Canonical Wnt signaling triggering -catenin-dependent gene expression contributes to cell cycle progression, in particular at the G1/S transition. Recently, however, it became clear that the cell cycle can also feed back on Wnt signaling at the G2/M transition. This is illustrated by the fact that mitosis-specific cyclin-dependent kinases can phosphorylate the Wnt co-receptor LRP6 to prime the pathway for incoming Wnt signals when cells enter mitosis. In addition, there is accumulating evidence that various Wnt pathway components might exert additional, Wnt-independent functions that are important for proper regulation of mitosis. The importance of Wnt pathways during mitosis was most recently enforced by the discovery of Wnt signaling contributing to the stabilization of proteins other than -catenin, specifically at G2/M and during mitosis. This Wnt-mediated stabilization of proteins, now referred to as Wnt/STOP, might on one hand contribute to maintaining a critical cell size required for cell division and, on the other hand, for the faithful execution of mitosis itself. In fact, most recently we have shown that Wnt/STOP is required for ensuring proper microtubule dynamics within mitotic spindles, which is pivotal for accurate chromosome segregation and for the maintenance of euploidy."],["dc.description.sponsorship","Deutsche Forschungsmeinschaft (DFG); [FOR942]"],["dc.identifier.doi","10.1080/15384101.2015.1064569"],["dc.identifier.isi","000360295400015"],["dc.identifier.pmid","26103566"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36289"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Taylor & Francis Inc"],["dc.relation.issn","1551-4005"],["dc.relation.issn","1538-4101"],["dc.title","Fresh WNT into the regulation of mitosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1704"],["dc.bibliographiccitation.journal","Biochemical Society Transactions"],["dc.bibliographiccitation.lastpage","1708"],["dc.bibliographiccitation.volume","38"],["dc.contributor.author","Stolz, Ailine"],["dc.contributor.author","Ertych, Norman"],["dc.contributor.author","Bastians, Holger"],["dc.date.accessioned","2018-11-07T08:36:02Z"],["dc.date.available","2018-11-07T08:36:02Z"],["dc.date.issued","2010"],["dc.description.abstract","CHK2 (checkpoint kinase 2) and BRCA1 (breast cancer early onset 1) are tumour suppressor genes that have been implicated previously in the DNA damage response Recently we have identified CHK2 and BRCA1 as genes required for the maintenance of chromosomal stability and have shown that a Chk2 mediated phosphorylation of Brca1 is required for the proper and timely assembly of mitotic spindles Loss of CHK2 BRCA1 or inhibition of its Chk2 mediated phosphorylation inevitably results in the transient formation of abnormal spindles that facilitate the establishment of faulty microtubule-kinetochore attachments associated with the generation of lagging chromosomes Importantly both CHK2 and BRCA1 are lost at very high frequency in aneuploid lung adenocarcinomas that are typically induced in knockout mice exhibiting chromosomal instability Thus these results suggest novel roles for Chk2 and Brca1 in mitosis that might contribute to their tumour suppressor functions"],["dc.identifier.doi","10.1042/BST0381704"],["dc.identifier.isi","000285813100055"],["dc.identifier.pmid","21118151"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/18214"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Portland Press Ltd"],["dc.relation.issn","0300-5127"],["dc.title","Loss of the tumour-suppressor genes CHK2 and BRCA1 results in chromosomal instability"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","779"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Nature Cell Biology"],["dc.bibliographiccitation.lastpage","U274"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Ertych, Norman"],["dc.contributor.author","Stolz, Ailine"],["dc.contributor.author","Stenzinger, Albrecht"],["dc.contributor.author","Weichert, Wilko"],["dc.contributor.author","Kaulfuss, Silke"],["dc.contributor.author","Burfeind, Peter"],["dc.contributor.author","Aigner, Achim"],["dc.contributor.author","Wordeman, Linda"],["dc.contributor.author","Bastians, Holger"],["dc.date.accessioned","2018-11-07T09:37:16Z"],["dc.date.available","2018-11-07T09:37:16Z"],["dc.date.issued","2014"],["dc.description.abstract","Chromosomal instability (CIN) is defined as the perpetual missegregation of whole chromosomes during mitosis and represents a hallmark of human cancer. However, the mechanisms influencing CIN and its consequences on tumour growth are largely unknown. We identified an increase in microtubule plus-end assembly rates as a mechanism influencing CIN in colorectal cancer cells. This phenotype is induced by overexpression of the oncogene AURKA or by loss of the tumour suppressor gene CHK2, a genetic constitution found in 73% of human colorectal cancers. Increased microtubule assembly rates are associated with transient abnormalities in mitotic spindle geometry promoting the generation of lagging chromosomes and influencing CIN. Reconstitution of proper microtubule assembly rates by chemical or genetic means suppresses CIN and thereby, unexpectedly, accelerates tumour growth in vitro and in vivo. Thus, we identify a fundamental mechanism influencing CIN in cancer cells and reveal its adverse consequence on tumour growth."],["dc.identifier.doi","10.1038/ncb2994"],["dc.identifier.isi","000339904900010"],["dc.identifier.pmid","24976383"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32803"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1476-4679"],["dc.relation.issn","1465-7392"],["dc.title","Increased microtubule assembly rates influence chromosomal instability in colorectal cancer cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","47061"],["dc.bibliographiccitation.issue","30"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","47081"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Schrader, Alexandra"],["dc.contributor.author","Meyer, Katharina"],["dc.contributor.author","Walther, Neele"],["dc.contributor.author","Stolz, Ailine"],["dc.contributor.author","Feist, Maren"],["dc.contributor.author","Hand, Elisabeth"],["dc.contributor.author","von Bonin, Frederike"],["dc.contributor.author","Evers, Maurits"],["dc.contributor.author","Kohler, Christian W."],["dc.contributor.author","Shirneshan, Katayoon"],["dc.contributor.author","Vockerodt, Martina"],["dc.contributor.author","Klapper, Wolfram"],["dc.contributor.author","Szczepanowski, Monika"],["dc.contributor.author","Murray, Paul G."],["dc.contributor.author","Bastians, Holger"],["dc.contributor.author","Truemper, Lorenz H."],["dc.contributor.author","Spang, Rainer"],["dc.contributor.author","Kube, Dieter"],["dc.date.accessioned","2018-11-07T10:11:28Z"],["dc.date.available","2018-11-07T10:11:28Z"],["dc.date.issued","2016"],["dc.description.abstract","To discover new regulatory pathways in B lymphoma cells, we performed a combined analysis of experimental, clinical and global gene expression data. We identified a specific cluster of genes that was coherently expressed in primary lymphoma samples and suppressed by activation of the B cell receptor (BCR) through aIgM treatment of lymphoma cells in vitro. This gene cluster, which we called BCR. 1, includes numerous cell cycle regulators. A reduced expression of BCR. 1 genes after BCR activation was observed in different cell lines and also in CD10(+) germinal center B cells. We found that BCR activation led to a delayed entry to and progression of mitosis and defects in metaphase. Cytogenetic changes were detected upon long-term aIgM treatment. Furthermore, an inverse correlation of BCR. 1 genes with c-Myc co-regulated genes in distinct groups of lymphoma patients was observed. Finally, we showed that the BCR. 1 index discriminates activated B cell-like and germinal centre B cell-like diffuse large B cell lymphoma supporting the functional relevance of this new regulatory circuit and the power of guided clustering for biomarker discovery."],["dc.identifier.doi","10.18632/oncotarget.9219"],["dc.identifier.isi","000385413000020"],["dc.identifier.pmid","27166259"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14137"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40052"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Impact Journals Llc"],["dc.relation.issn","1949-2553"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.title","Identification of a new gene regulatory circuit involving B cell receptor activated signaling using a combined analysis of experimental, clinical and global gene expression data"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]