Ahlen, Melanie von

[["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","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"]]