Holembowski, Lena

[["dc.bibliographiccitation.firstpage","275"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Experimental Medicine"],["dc.bibliographiccitation.lastpage","289"],["dc.bibliographiccitation.volume","209"],["dc.contributor.author","Schulz, Ramona"],["dc.contributor.author","Marchenko, Natalia D."],["dc.contributor.author","Holembowski, Lena"],["dc.contributor.author","Fingerle-Rowson, Guenter"],["dc.contributor.author","Pesic, Marina"],["dc.contributor.author","Zender, Lars"],["dc.contributor.author","Dobbelstein, Matthias"],["dc.contributor.author","Moll, Ute M."],["dc.date.accessioned","2018-11-07T09:13:28Z"],["dc.date.available","2018-11-07T09:13:28Z"],["dc.date.issued","2012"],["dc.description.abstract","Intracellular macrophage migration inhibitory factor (MIF) often becomes stabilized in human cancer cells. MIF can promote tumor cell survival, and elevated MIF protein correlates with tumor aggressiveness and poor prognosis. However, the molecular mechanism facilitating MIF stabilization in tumors is not understood. We show that the tumor-activated HSP90 chaperone complex protects MIF from degradation. Pharmacological inhibition of HSP90 activity, or siRNA-mediated knockdown of HSP90 or HDAC6, destabilizes MIF in a variety of human cancer cells. The HSP90-associated E3 ubiquitin ligase CHIP mediates the ensuing proteasome-dependent MIF degradation. Cancer cells contain constitutive endogenous MIF-HSP90 complexes. siRNA-mediated MIF knockdown inhibits proliferation and triggers apoptosis of cultured human cancer cells, whereas HSP90 inhibitor-induced apoptosis is overridden by ectopic MIF expression. In the ErbB2 transgenic model of human HER2-positive breast cancer, genetic ablation of MIF delays tumor progression and prolongs overall survival of mice. Systemic treatment with the HSP90 inhibitor 17AAG reduces MIF expression and blocks growth of MIF-expressing, but not MIF-deficient, tumors. Together, these findings identify MIF as a novel HSP90 client and suggest that HSP90 inhibitors inhibit ErbB2-driven breast tumor growth at least in part by destabilizing MIF."],["dc.identifier.doi","10.1084/jem.20111117"],["dc.identifier.isi","000301943200009"],["dc.identifier.pmid","22271573"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10625"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/27181"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Rockefeller Univ Press"],["dc.relation.issn","0022-1007"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Inhibiting the HSP90 chaperone destabilizes macrophage migration inhibitory factor and thereby inhibits breast tumor progression"],["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"]]

[["dc.bibliographiccitation.firstpage","640"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Experimental Medicine"],["dc.bibliographiccitation.lastpage","640"],["dc.bibliographiccitation.volume","209"],["dc.contributor.author","Schulz, Ramona"],["dc.contributor.author","Marchenko, Natalia D."],["dc.contributor.author","Holembowski, Lena"],["dc.contributor.author","Fingerle-Rowson, Günter"],["dc.contributor.author","Pesic, Marina"],["dc.contributor.author","Zender, Lars"],["dc.contributor.author","Dobbelstein, Matthias"],["dc.contributor.author","Mol, Ute M."],["dc.date.accessioned","2022-03-01T11:46:34Z"],["dc.date.available","2022-03-01T11:46:34Z"],["dc.date.issued","2012"],["dc.identifier.doi","10.1084/jem.201111172093c"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103714"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.eissn","1540-9538"],["dc.relation.issn","0022-1007"],["dc.title","Inhibiting the HSP90 chaperone destabilizes macrophage migration inhibitory factor and thereby inhibits breast tumor progression"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","680"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Cell Cycle"],["dc.bibliographiccitation.lastpage","689"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Holembowski, Lena"],["dc.contributor.author","Schulz, Ramona"],["dc.contributor.author","Talos, Flaminia"],["dc.contributor.author","Scheel, Andreas"],["dc.contributor.author","Holzman, Sonja"],["dc.contributor.author","Dobbelstein, Matthias"],["dc.contributor.author","Moll, Ute M."],["dc.date.accessioned","2018-11-07T08:59:14Z"],["dc.date.available","2018-11-07T08:59:14Z"],["dc.date.issued","2011"],["dc.description.abstract","The ancient p53 paralogs p63 and p73 regulate specific tissue formation, cell survival and cell death via their TA and Delta N isoforms. Targeted disruption of the p73 locus leads to severe defects in the development of the central nervous system (CNS), and p73 has recently been shown to be an essential regulator of neural stem cell maintenance and differentiation in both embryonal and adult neurogenesis. In contrast, global p63(-/-) mice lack skin and limbs. Moreover, p63 is detectable in embryonic cortex. It has previously been proposed to also play critical pro-death and pro-survival roles in neural precursors of the developing sympathetic and central nervous system, respectively, based on experimental overexpression and siRNA-mediated knockdown of p63. Here we perform an extensive analysis of the developing central nervous system in global p63(-/-) mice and their wildtype littermates. Brain and spinal cord of embryos and newborn mice were assessed in vivo for neuroanatomy, histology, apoptosis, proliferation, stemness and differentiation, and in vitro for self-renewal and maturation in neurosphere assays. None of these analyses revealed a detectable phenotype in p63(-/-) mice. Hence, despite the profound impact of p63 on the development of stratified epithelia and limbs, p63 is completely dispensable for proper development of the central nervous system. Thus, despite their strong homology, the non-overlapping tissue specificity of p63 and p73 functions appears more pronounced than previously anticipated."],["dc.identifier.doi","10.4161/cc.10.4.14859"],["dc.identifier.isi","000287352500026"],["dc.identifier.pmid","21293190"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/23841"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Landes Bioscience"],["dc.relation.issn","1538-4101"],["dc.title","While p73 is essential, p63 is completely dispensable for the development of the central nervous system"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1816"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Cell Death and Differentiation"],["dc.bibliographiccitation.lastpage","1829"],["dc.bibliographiccitation.volume","17"],["dc.contributor.author","Talos, F."],["dc.contributor.author","Abraham, A."],["dc.contributor.author","Vaseva, A. V."],["dc.contributor.author","Holembowski, L."],["dc.contributor.author","Tsirka, S. E."],["dc.contributor.author","Scheel, A."],["dc.contributor.author","Bode, D."],["dc.contributor.author","Dobbelstein, M."],["dc.contributor.author","Brück, W."],["dc.contributor.author","Moll, U. M."],["dc.date.accessioned","2018-11-07T08:36:04Z"],["dc.date.available","2018-11-07T08:36:04Z"],["dc.date.issued","2010"],["dc.description.abstract","The p53 family member p73 is essential for brain development, but its precise role and scope remain unclear. Global p73 deficiency determines an overt and highly penetrant brain phenotype marked by cortical hypoplasia with ensuing hydrocephalus and hippocampal dysgenesis. The Delta Np73 isoform is known to function as a prosurvival factor of mature postmitotic neurons. In this study, we define a novel essential role of p73 in the regulation of the neural stem cell compartment. In both embryonic and adult neurogenesis, p73 has a critical role in maintaining an adequate neurogenic pool by promoting self-renewal and proliferation and inhibiting premature senescence of neural stem and early progenitor cells. Thus, products of the p73 gene locus are essential maintenance factors in the central nervous system, whose broad action stretches across the entire differentiation arch from stem cells to mature postmitotic neurons. Cell Death and Differentiation (2010) 17, 1816-1829; doi:10.1038/cdd.2010.131"],["dc.identifier.doi","10.1038/cdd.2010.131"],["dc.identifier.isi","000284209600003"],["dc.identifier.pmid","21076477"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/18221"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.notes.submitter","Najko"],["dc.relation.issn","1350-9047"],["dc.title","p73 is an essential regulator of neural stem cell maintenance in embryonal and adult CNS neurogenesis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1173"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","The Journal of Cell Biology"],["dc.bibliographiccitation.lastpage","1190"],["dc.bibliographiccitation.volume","204"],["dc.contributor.author","Holembowski, Lena"],["dc.contributor.author","Kramer, Daniela"],["dc.contributor.author","Riedel, Dietmar"],["dc.contributor.author","Sordella, Raffaella"],["dc.contributor.author","Nemajerova, Alice"],["dc.contributor.author","Dobbelstein, Matthias"],["dc.contributor.author","Moll, Ute M."],["dc.date.accessioned","2018-11-07T09:42:22Z"],["dc.date.available","2018-11-07T09:42:22Z"],["dc.date.issued","2014"],["dc.description.abstract","A core evolutionary function of the p53 family is to protect the genomic integrity of gametes. However, the role of p73 in the male germ line is unknown. Here, we reveal that TAp73 unexpectedly functions as an adhesion and maturation factor of the seminiferous epithelium orchestrating spermiogenesis. TAp73 knockout (TAp73KO) and p73KO mice, but not. Np73KO mice, display a \"near-empty seminiferous tubule\" phenotype due to massive premature loss of immature germ cells. The cellular basis of this phenotype is defective cell-cell adhesions of developing germ cells to Sertoli nurse cells, with likely secondary degeneration of Sertoli cells, including the blood-testis barrier, which leads to disruption of the adhesive integrity and maturation of the germ epithelium. At the molecular level, TAp73, which is produced in germ cells, controls a coordinated transcriptional program of adhesion-and migrationrelated proteins including peptidase inhibitors, proteases, receptors, and integrins required for germ-Sertoli cell adhesion and dynamic junctional restructuring. Thus, we propose the testis as a unique organ with strict division of labor among all family members: p63 and p53 safeguard germ line fidelity, whereas TAp73 ensures fertility by enabling sperm maturation."],["dc.description.sponsorship","National Cancer Institute [CA93853]; Deutsche Krebshilfe [108775]"],["dc.identifier.doi","10.1083/jcb.201306066"],["dc.identifier.isi","000333903600010"],["dc.identifier.pmid","24662569"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/33940"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Rockefeller Univ Press"],["dc.relation.issn","1540-8140"],["dc.relation.issn","0021-9525"],["dc.title","TAp73 is essential for germ cell adhesion and maturation in testis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]