Ninković, Milena

[["dc.bibliographiccitation.artnumber","201"],["dc.bibliographiccitation.journal","Frontiers in physiology"],["dc.bibliographiccitation.volume","4"],["dc.contributor.author","Herrmann, Solveig"],["dc.contributor.author","Ninkovic, Milena"],["dc.contributor.author","Kohl, Tobias"],["dc.contributor.author","Pardo, Luis A."],["dc.date.accessioned","2019-07-09T11:40:08Z"],["dc.date.available","2019-07-09T11:40:08Z"],["dc.date.issued","2013"],["dc.description.abstract","Although crucial for their correct function, the mechanisms controlling surface expression of ion channels are poorly understood. In the case of the voltage-gated potassium channel KV10.1, this is determinant not only for its physiological function in brain, but also for its pathophysiology in tumors and possible use as a therapeutic target. The Golgi resident protein PIST binds several membrane proteins, thereby modulating their expression. Here we describe a PDZ domain-mediated interaction of KV10.1 and PIST, which enhances surface levels of KV10.1. The functional, but not the physical interaction of both proteins is dependent on the coiled-coil and PDZ domains of PIST; insertion of eight amino acids in the coiled-coil domain to render the neural form of PIST (nPIST) and the corresponding short isoform in an as-of-yet unknown form abolishes the effect. In addition, two new isoforms of PIST (sPIST and nsPIST) lacking nearly the complete PDZ domain were cloned and shown to be ubiquitously expressed. PIST and KV10.1 co-precipitate from native and expression systems. nPIST also showed interaction, but did not alter the functional expression of the channel. We could not document physical interaction between KV10.1 and sPIST, but it reduced KV10.1 functional expression in a dominant-negative manner. nsPIST showed weak physical interaction and no functional effect on KV10.1. We propose these isoforms to work as modulators of PIST function via regulating the binding on interaction partners."],["dc.identifier.doi","10.3389/fphys.2013.00201"],["dc.identifier.fs","604131"],["dc.identifier.pmid","23966943"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10690"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58100"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1664-042X"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.title","PIST (GOPC) modulates the oncogenic voltage-gated potassium channel KV10.1."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","96697"],["dc.bibliographiccitation.firstpage","96697"],["dc.bibliographiccitation.issue","57"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","96709"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Sperling, Swetlana"],["dc.contributor.author","Aung, Thiha"],["dc.contributor.author","Martin, Sabine"],["dc.contributor.author","Rohde, Veit"],["dc.contributor.author","Ninkovic, Milena"],["dc.date.accessioned","2018-10-09T07:07:52Z"],["dc.date.available","2018-10-09T07:07:52Z"],["dc.date.issued","2017-11-14"],["dc.description.abstract","A small subpopulation of tumor stem-like cells has the capacity to initiate tumors and mediate radio- and chemoresistance in diverse cancers hence also in glioblastoma (GBM). It has been reported that this capacity of tumor initiation in the brain is mainly dependent on the body's nutrient supply. This population of so-called brain tumor initiating or brain tumor stem-like cells (BTSCs) is able to extract nutrients like glucose with a higher affinity. Riluzole, a drug approved for treating amyotrophic lateral sclerosis (ALS), was reported to possess anticancer properties, affecting the glutamate metabolism. We report that riluzole treatment inhibits the growth of brain tumor stem-like cells enriched cultures isolated from two human glioblastomas. The effects of riluzole on these cells were associated with an inhibition of a poor prognostic indicator: glucose transporter 3 (GLUT3). A decrease in GLUT3 is associated with a decrease in the p-Akt/HIF1α pathway. Further, downregulation of the DNA (Cytosine-5-)-methyltransferase 1 (DNMT1) gene that causes hypermethylation of various tumor-suppressor genes and leads to a poor prognosis in GBM, was detected. Two hallmarks of cancer cells-proliferation and cell death-were positively influenced by riluzole treatment. Finally, we observed that riluzole reduced the tumor growth in in vivo CAM assay, suggesting it could be a possible synergistic drug for the treatment of glioblastoma."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2017"],["dc.fs.pkfprnr","86427"],["dc.identifier.doi","10.18632/oncotarget.18043"],["dc.identifier.fs","633522"],["dc.identifier.pmid","29228563"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14509"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/15891"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation.eissn","1949-2553"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Riluzole: a potential therapeutic intervention in human brain tumor stem-like cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]