Wottawa, Marieke

[["dc.bibliographiccitation.firstpage","3610"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Blood"],["dc.bibliographiccitation.lastpage","3617"],["dc.bibliographiccitation.volume","110"],["dc.contributor.author","Koditz, Jens"],["dc.contributor.author","Nesper, Jutta"],["dc.contributor.author","Wottawa, Marieke"],["dc.contributor.author","Stiehl, Daniel P."],["dc.contributor.author","Camenisch, Gieri"],["dc.contributor.author","Franke, Corinna"],["dc.contributor.author","Myllyharju, Johanna"],["dc.contributor.author","Wenger, Roland H."],["dc.contributor.author","Katschinski, Doerthe Magdalena"],["dc.date.accessioned","2018-11-07T10:53:15Z"],["dc.date.available","2018-11-07T10:53:15Z"],["dc.date.issued","2007"],["dc.description.abstract","The activating transcription factor-4 (ATF-4) is translationally induced under anoxic conditions, mediates part of the unfolded protein response following endoplasmic reticulum (ER) stress, and is a critical regulator of cell fate. Here, we identified the zipper 11 domain of ATF-4 to interact with the oxygen sensor prolyl-4-hydroxylase domain 3 (PHD3). The PHD inhibitors dimethyloxalylglycine (DMOG) and hypoxia, or proteasomal inhibition, all induced ATF-4 protein levels. Hypoxic induction of ATF-4 was due to increased protein stability, but was independent of the ubiquitin ligase von Hippel-Lindau protein (pVHL).,A novel oxygen-dependent degradation (ODD) domain was identified adjacent to the zipper 11 domain. Mutations of 5 prolyl residues within this ODD domain or siRNA-mediated down-regulation of PHD3, but not of PHD2, was sufficient to stabilize ATF-4 under normoxic conditions. These data demonstrate that PHD-dependent oxygen-sensing recruits both the hypoxia-inducible factor (HIF) and ATF-4 systems, and hence not only confers adaptive responses but also cell fate decisions."],["dc.identifier.doi","10.1182/blood-2007-06-094441"],["dc.identifier.isi","000250946300026"],["dc.identifier.pmid","17684156"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/49312"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Hematology"],["dc.relation.issn","0006-4971"],["dc.title","Oxygen-dependent ATF-4 stability is mediated by the PHD3 oxygen sensor"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Annals of Oncology"],["dc.bibliographiccitation.volume","27"],["dc.contributor.author","Kozlova, Nina"],["dc.contributor.author","Wottawa, Marieke"],["dc.contributor.author","Katschinski, Doerthe Magdalena"],["dc.contributor.author","Kristiansen, Glen"],["dc.contributor.author","Kietzmann, Thomas"],["dc.date.accessioned","2018-11-07T10:07:18Z"],["dc.date.available","2018-11-07T10:07:18Z"],["dc.date.issued","2016"],["dc.identifier.doi","10.1093/annonc/mdw362.27"],["dc.identifier.isi","000393912500028"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/39250"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.publisher.place","Oxford"],["dc.relation.conference","41st Congress of the European-Society-for-Medical-Oncology (ESMO)"],["dc.relation.eventlocation","Copenhagen, DENMARK"],["dc.relation.issn","1569-8041"],["dc.relation.issn","0923-7534"],["dc.title","Hypoxia inducible factor prolyl hydroxylase 2 (PHD2) is a direct regulator of epidermal growth factor receptor (EGFR) signaling in breast cancer"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","33756"],["dc.bibliographiccitation.issue","44"],["dc.bibliographiccitation.journal","Journal of Biological Chemistry"],["dc.bibliographiccitation.lastpage","33763"],["dc.bibliographiccitation.volume","285"],["dc.contributor.author","Vogel, Sabine"],["dc.contributor.author","Wottawa, Marieke"],["dc.contributor.author","Farhat, Katja"],["dc.contributor.author","Zieseniss, Anke"],["dc.contributor.author","Schnelle, Moritz"],["dc.contributor.author","Le-Huu, Sinja"],["dc.contributor.author","von Ahlen, Melanie"],["dc.contributor.author","Malz, Cordula R."],["dc.contributor.author","Camenisch, Gieri"],["dc.contributor.author","Katschinski, Doerthe Magdalena"],["dc.date.accessioned","2018-11-07T08:37:53Z"],["dc.date.available","2018-11-07T08:37:53Z"],["dc.date.issued","2010"],["dc.description.abstract","Cells are responding to hypoxia via prolyl-4-hydroxylase domain (PHD) enzymes, which are responsible for oxygen-dependent hydroxylation of the hypoxia-inducible factor (HIF)-1 alpha subunit. To gain further insight into PHD function, we generated knockdown cell models for the PHD2 isoform, which is the main isoform regulating HIF-1 alpha hydroxylation and thus stability in normoxia. Induction of a PHD2 knockdown in tetracycline-inducible HeLa PHD2 knockdown cells resulted in increased F-actin formation as detected by phalloidin staining. A similar effect could be observed in the stably transfected PHD2 knockdown cell clones 1B6 and 3B7. F-actin is at least in part responsible for shaping cell morphology as well as regulating cell migration. Cell migration was impaired significantly as a consequence of PHD2 knockdown in a scratch assay. Mechanistically, PHD2 knockdown resulted in activation of the RhoA (Ras homolog gene family member A)/Rho-associated kinase pathway with subsequent phosphorylation of cofilin. Because cofilin phosphorylation impairs its actin-severing function, this may explain the F-actin phenotype, thereby providing a functional link between PHD2-dependent signaling and cell motility."],["dc.identifier.doi","10.1074/jbc.M110.132985"],["dc.identifier.isi","000283354000021"],["dc.identifier.pmid","20801873"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6193"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/18648"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Biochemistry Molecular Biology Inc"],["dc.relation.issn","0021-9258"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Prolyl Hydroxylase Domain (PHD) 2 Affects Cell Migration and F-actin Formation via RhoA/Rho-associated Kinase-dependent Cofilin Phosphorylation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","365"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Leukocyte Biology"],["dc.bibliographiccitation.lastpage","375"],["dc.bibliographiccitation.volume","96"],["dc.contributor.author","Swain, Lija"],["dc.contributor.author","Wottawa, Marieke"],["dc.contributor.author","Hillemann, Annette"],["dc.contributor.author","Beneke, Angelika"],["dc.contributor.author","Odagiri, Haruki"],["dc.contributor.author","Terada, Kazutoyo"],["dc.contributor.author","Endo, Motoyoshi"],["dc.contributor.author","Oike, Yuichi"],["dc.contributor.author","Farhat, Katja"],["dc.contributor.author","Katschinski, Doerthe Magdalena"],["dc.date.accessioned","2018-11-07T09:36:09Z"],["dc.date.available","2018-11-07T09:36:09Z"],["dc.date.issued","2014"],["dc.description.abstract","On a molecular level, cells sense changes in oxygen availability through the PHDs, which regulate the protein stability of the alpha-subunit of the transcription factor HIF. Especially, PHD3 has been additionally associated with apoptotic cell death. We hypothesized that PHD3 plays a role in cell-fate decisions in macrophages. Therefore, myeloid-specific PHD3(-/-) mice were created and analyzed. PHD3(-/-) BMDM showed no altered HIF-1 alpha or HIF-2 alpha stabilization or increased HIF target gene expression in normoxia or hypoxia. Macrophage M1 and M2 polarization was unchanged likewise. Compared with macrophages from WT littermates, PHD3(-/-) BMDM exhibited a significant reduction in TUNEL-positive cells after serum withdrawal or treatment with stauro and SNAP. Under the same conditions, PHD3(-/-) BMDM also showed less Annexin V staining, which is representative for membrane disruption, and indicated a reduced early apoptosis. In an unbiased transcriptome screen, we found that Angptl2 expression was reduced in PHD3(-/-) BMDM under stress conditions. Addition of rAngptl2 rescued the antiapoptotic phenotype, demonstrating that it is involved in the PHD3-mediated response toward apoptotic stimuli in macrophages."],["dc.identifier.doi","10.1189/jlb.2HI1013-533R"],["dc.identifier.isi","000340829400003"],["dc.identifier.pmid","24626957"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32548"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Federation Amer Soc Exp Biol"],["dc.relation.issn","1938-3673"],["dc.relation.issn","0741-5400"],["dc.title","Prolyl-4-hydroxylase domain 3 (PHD3) is a critical terminator for cell survival of macrophages under stress conditions"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2787"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","International Journal of Cancer"],["dc.bibliographiccitation.lastpage","2798"],["dc.bibliographiccitation.volume","132"],["dc.contributor.author","Wottawa, Marieke"],["dc.contributor.author","Leisering, Pia"],["dc.contributor.author","von Ahlen, Melanie"],["dc.contributor.author","Schnelle, Moritz"],["dc.contributor.author","Vogel, Sabine"],["dc.contributor.author","Malz, Cordula R."],["dc.contributor.author","Bordoli, Mattia Renato"],["dc.contributor.author","Camenisch, Gieri"],["dc.contributor.author","Hesse, Amke"],["dc.contributor.author","Napp, Joanna"],["dc.contributor.author","Alves, Frauke"],["dc.contributor.author","Kristiansen, Glen"],["dc.contributor.author","Farhat, Katja"],["dc.contributor.author","Katschinski, Doerthe Magdalena"],["dc.date.accessioned","2018-11-07T09:23:40Z"],["dc.date.available","2018-11-07T09:23:40Z"],["dc.date.issued","2013"],["dc.description.abstract","The prolyl-4-hydroxylase domain 13 (PHD13) enzymes are regulating the protein stability of the -subunit of the hypoxia-inducible factor-1 (HIF-1), which mediates oxygen-dependent gene expression. PHD2 is the main isoform regulating HIF-1 hydroxylation and thus stability in normoxia. In human cancers, HIF-1 is overexpressed as a result of intratumoral hypoxia which in turn promotes tumor progression. The role of PHD2 for tumor progression is in contrast far from being thoroughly understood. Therefore, we established PHD2 knockdown clones of MDA-MB-231 breast cancer cells and analyzed their tumor-forming potential in a SCID mouse model. Tumor progression was significantly impaired in the PHD2 knockdown MDA-MB-231 cells, which could be partially rescued by re-establishing PHD2 expression. In a RNA profile screen, we identified the secreted phosphoprotein 1 (SPP1) as one target, which is differentially regulated as a consequence of the PHD2 knockdown. Knockdown of PHD2 drastically reduced the SPP1 expression in MDA-MB-231 cells. A correlation of SPP1 and PHD2 expression was additionally verified in 294 invasive breast cancer biopsies. In subsequent analyses, we identified that PHD2 alters the processing of transforming growth factor (TGF)-1, which is highly involved in SPP1 expression. The altered processing capacity was associated with a dislocation of the pro-protein convertase furin. Thus, our data demonstrate that in MDA-MB-231 cells PHD2 might affect tumor-relevant TGF-1 target gene expression by altering the TGF-1 processing capacity."],["dc.description.sponsorship","Wilhelm Sander Stiftung [1348530]"],["dc.identifier.doi","10.1002/ijc.27982"],["dc.identifier.isi","000317593100008"],["dc.identifier.pmid","23225569"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29634"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","0020-7136"],["dc.title","Knockdown of prolyl-4-hydroxylase domain 2 inhibits tumor growth of human breast cancer MDA-MB-231 cells by affecting TGF-1 processing"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","9885"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","9898"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Kozlova, Nina"],["dc.contributor.author","Wottawa, Marieke"],["dc.contributor.author","Katschinski, Doerthe Magdalena"],["dc.contributor.author","Kristiansen, Glen"],["dc.contributor.author","Kietzmann, Thomas"],["dc.date.accessioned","2018-11-07T10:27:32Z"],["dc.date.available","2018-11-07T10:27:32Z"],["dc.date.issued","2017"],["dc.description.abstract","Clinical studies in breast cancer suggest important associations between intratumoral hypoxia, the upregulation of epidermal growth factor receptor (EGFR or HER1), hypoxia-inducible factor 1 alpha (HIF-1 alpha), and reduced patient survival. However, direct molecular links between EGFR and the hypoxia signaling system are not yet established. Since the oxygen sensor hypoxia-inducible factor prolyl hydroxylase 2 (PHD2) is considered to be the main HIF-1 alpha regulator, we hypothesized that PHD2 and EGFR may be interconnected at the molecular level. By analyzing samples from 313 breast cancer patients, we found that EGFR is a first clinicopathological parameter positively correlating with PHD2. Mechanistically, we identified PHD2 as a direct binding partner of EGFR and show that PHD2 regulates EGFR stability as well as its subsequent signaling in breast carcinoma cells. Overall, we introduce for the first time the direct crosstalk between the oxygen sensor PHD2 and EGFR-mediated tumorigenesis in breast cancer."],["dc.identifier.doi","10.18632/oncotarget.14241"],["dc.identifier.isi","000394181800080"],["dc.identifier.pmid","28038470"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43251"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Impact Journals Llc"],["dc.relation.issn","1949-2553"],["dc.title","Hypoxia-inducible factor prolyl hydroxylase 2 (PHD2) is a direct regulator of epidermal growth factor receptor (EGFR) signaling in breast cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Acta Physiologica"],["dc.bibliographiccitation.volume","210"],["dc.contributor.author","Wottawa, Marieke"],["dc.contributor.author","Boettger, J."],["dc.contributor.author","von Ahlen, Melanie"],["dc.contributor.author","Katschinski, Doerthe Magdalena"],["dc.date.accessioned","2018-11-07T09:42:48Z"],["dc.date.available","2018-11-07T09:42:48Z"],["dc.date.issued","2014"],["dc.format.extent","130"],["dc.identifier.isi","000332259900336"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34040"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.publisher.place","Hoboken"],["dc.relation.issn","1748-1716"],["dc.relation.issn","1748-1708"],["dc.title","Quantitative proteomic analysis of the plasma membrane protein composition in hypoxia"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","9039"],["dc.bibliographiccitation.issue","23"],["dc.bibliographiccitation.journal","Analytical Chemistry"],["dc.bibliographiccitation.lastpage","9046"],["dc.bibliographiccitation.volume","83"],["dc.contributor.author","Napp, Joanna"],["dc.contributor.author","Behnke, Thomas"],["dc.contributor.author","Fischer, Lorenz"],["dc.contributor.author","Wuerth, Christian"],["dc.contributor.author","Wottawa, Marieke"],["dc.contributor.author","Katschinski, Doerthe Magdalena"],["dc.contributor.author","Alves, Frauke"],["dc.contributor.author","Resch-Genger, Ute"],["dc.contributor.author","Schaeferling, Michael"],["dc.date.accessioned","2018-11-07T08:49:19Z"],["dc.date.available","2018-11-07T08:49:19Z"],["dc.date.issued","2011"],["dc.description.abstract","Polystyrene nanoparticles (PS-NPs) were doped with an oxygen-sensitive near-infrared (NIR)-emissive palladium meso-tetraphenylporphyrin and an inert reference dye which are both excitable at 635 nm. The nanosensors were characterized with special emphasis on fundamental parameters such as absolute photoluminescence quantum yield and fluorescence lifetime. The PS-NPs were employed for ratiometric dual-wavelength and lifetime-based photoluminescent oxygen sensing. They were efficiently taken up by cultured murine alveolar macrophages, yielding a characteristic and reversible change in ratiometric response with decreasing oxygen concentration. This correlated with the cellular hypoxic status verified by analysis of hypoxia inducible factor-1 alpha (HIF-1 alpha) accumulation. In addition, the surface of PS-NPs was functionalized with polyethylene glycol (PEG) and the monoclonal antibody herceptin, and their binding to HER2/neu-overexpressing tumor cells was confirmed in vitro. First experiments with tumor-bearing mouse revealed a distinctive ratiometric response within the tumor upon hypoxic condition induced by animal sacrifice. These results demonstrate the potential of these referenced NIR nanosensors for in vitro and in vivo imaging that present a new generation of optical probes for oncology."],["dc.identifier.doi","10.1021/ac201870b"],["dc.identifier.isi","000297481700032"],["dc.identifier.pmid","22007722"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/21431"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Chemical Soc"],["dc.relation.issn","1520-6882"],["dc.relation.issn","0003-2700"],["dc.title","Targeted Luminescent Near-Infrared Polymer-Nanoprobes for In Vivo Imaging of Tumor Hypoxia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Acta Physiologica"],["dc.bibliographiccitation.volume","213"],["dc.contributor.author","Naas, S."],["dc.contributor.author","Wottawa, Marieke"],["dc.contributor.author","Boettger, J."],["dc.contributor.author","Kroehnert, K."],["dc.contributor.author","Rizzoli, Silvio"],["dc.contributor.author","Katschinski, Doerthe Magdalena"],["dc.date.accessioned","2018-11-07T09:59:51Z"],["dc.date.available","2018-11-07T09:59:51Z"],["dc.date.issued","2015"],["dc.format.extent","78"],["dc.identifier.isi","000362554200165"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37683"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.publisher.place","Hoboken"],["dc.relation.issn","1748-1716"],["dc.relation.issn","1748-1708"],["dc.title","Hypoxia alters trans-Golgi associated endocytosis independent from the Hypoxia-inducible factor-1"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","457"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Acta Physiologica"],["dc.bibliographiccitation.lastpage","463"],["dc.bibliographiccitation.volume","198"],["dc.contributor.author","Wottawa, Marieke"],["dc.contributor.author","Koeditz, Jens"],["dc.contributor.author","Katschinski, Doerthe Magdalena"],["dc.date.accessioned","2018-11-07T08:44:14Z"],["dc.date.available","2018-11-07T08:44:14Z"],["dc.date.issued","2010"],["dc.description.abstract","Aim: Hypoxia-inducible gene expression is an important physiological adaptive mechanism in response to a decreased oxygen supply. We have recently described an oxygen- and prolyl-4-hydroxylase (PHD)3-dependent stabilization of the activating transcription factor 4 (ATF-4). The aim of the present study was to examine if the normoxic destabilization of ATF-4 is regulated by oxygen-dependent proteasomal degradation. Methods: We determined poly-ubiquitination of ATF-4 in normoxia compared to hypoxia by immunoprecipitation and immunoblots. Furthermore, we analysed the expression of the ATF-4 target gene GADD153 as a function of oxygen concentration. Results: ATF-4 protein levels were not detectable in normoxia. Normoxic degradation correlated with an oxygen-dependent poly-ubiquitination of ATF-4, which was hindered by hypoxic incubation of the cells. As a result of hypoxia, GADD153 was expressed. The hypoxic GADD153 expression was attenuated or increased by transfecting the cells with ATF-4 siRNA or PHD3 siRNA respectively. Conclusion: Our results demonstrate the involvement of oxygen-dependent proteasomal degradation of ATF-4 in the hypoxia-induced expression of GADD153. Taken together, hypoxia/PHD3-regulated stabilization of ATF-4 by hindering oxygen-dependent degradation may play a critical role in linking cell fate decisions to oxygen availability."],["dc.identifier.doi","10.1111/j.1748-1716.2009.02060.x"],["dc.identifier.isi","000275216200006"],["dc.identifier.pmid","19922526"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/20153"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell Publishing, Inc"],["dc.relation.issn","1748-1708"],["dc.title","Normoxic destabilization of ATF-4 depends on proteasomal degradation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]