Moll, Ute M.

[["dc.bibliographiccitation.firstpage","1718"],["dc.bibliographiccitation.issue","14"],["dc.bibliographiccitation.journal","Cell Cycle"],["dc.bibliographiccitation.lastpage","1723"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Marchenko, Natasha D."],["dc.contributor.author","Moll, Ute M."],["dc.date.accessioned","2018-11-07T11:00:37Z"],["dc.date.available","2018-11-07T11:00:37Z"],["dc.date.issued","2007"],["dc.description.abstract","p53 ubiquitination at C-terminal lysines by MDM2 and other E3 ligases had been considered a straightforward negative regulation of p53 with only one function, that is marking the protein for proteasomal degradation. In this review, we will focus on the recently uncovered activating role of ubiquitination in the transcription-independent direct mitochondrial death program of p53."],["dc.identifier.isi","000249091300009"],["dc.identifier.pmid","17630506"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/50963"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Landes Bioscience"],["dc.relation.issn","1538-4101"],["dc.title","The role of ubiquitination in the direct mitochondrial death program of p53"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","780"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Cell Death and Differentiation"],["dc.bibliographiccitation.lastpage","780"],["dc.bibliographiccitation.volume","26"],["dc.contributor.author","Kramer, Daniela"],["dc.contributor.author","Stark, Nadine"],["dc.contributor.author","Schulz-Heddergott, Ramona"],["dc.contributor.author","Erytch, Norman"],["dc.contributor.author","Edmunds, Shelley"],["dc.contributor.author","Roßmann, Laura"],["dc.contributor.author","Bastians, Holger"],["dc.contributor.author","Concin, Nicole"],["dc.contributor.author","Moll, Ute M."],["dc.contributor.author","Dobbelstein, Matthias"],["dc.date.accessioned","2020-12-10T18:09:42Z"],["dc.date.available","2020-12-10T18:09:42Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1038/s41418-018-0190-8"],["dc.identifier.eissn","1476-5403"],["dc.identifier.issn","1350-9047"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/73731"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.relation.iserratumof","/handle/2/43281"],["dc.title","Correction: Strong antitumor synergy between DNA crosslinking and HSP90 inhibition causes massive premitotic DNA fragmentation in ovarian cancer cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","erratum_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","300"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Cell Death and Differentiation"],["dc.bibliographiccitation.lastpage","316"],["dc.bibliographiccitation.volume","24"],["dc.contributor.author","Kramer, Daniela"],["dc.contributor.author","Stark, Nadine"],["dc.contributor.author","Schulz-Heddergott, Ramona"],["dc.contributor.author","Erytch, Norman"],["dc.contributor.author","Edmunds, Shelley"],["dc.contributor.author","Rossmann, Laura"],["dc.contributor.author","Bastians, Holger"],["dc.contributor.author","Concin, Nicole"],["dc.contributor.author","Moll, Ute M."],["dc.contributor.author","Dobbelstein, Matthias"],["dc.date.accessioned","2018-11-07T10:27:41Z"],["dc.date.available","2018-11-07T10:27:41Z"],["dc.date.issued","2017"],["dc.description.abstract","All current regimens for treating ovarian cancer center around carboplatin as standard first line. The HSP90 inhibitor ganetespib is currently being assessed in advanced clinical oncology trials. Thus, we tested the combined effects of ganetespib and carboplatin on a panel of 15 human ovarian cancer lines. Strikingly, the two drugs strongly synergized in cytotoxicity in tumor cells lacking wild-type p53. Mechanistically, ganetespib and carboplatin in combination, but not individually, induced persistent DNA damage causing massive global chromosome fragmentation. Live-cell microscopy revealed chromosome fragmentation occurring to a dramatic degree when cells condensed their chromatin in preparation for mitosis, followed by cell death in mitosis or upon aberrant exit from mitosis. HSP90 inhibition caused the rapid decay of key components of the Fanconi anemia pathway required for repair of carboplatin-induced interstrand crosslinks (ICLs), as well as of cell cycle checkpoint mediators. Overexpressing FancA rescued the DNA damage induced by the drug combination, indicating that FancA is indeed a key client of Hsp90 that enables cancer cell survival in the presence of ICLs. Conversely, depletion of nuclease DNA2 prevented chromosomal fragmentation, pointing to an imbalance of defective repair in the face of uncontrolled nuclease activity as mechanistic basis for the observed premitotic DNA fragmentation. Importantly, the drug combination induced robust antitumor activity in xenograft models, again accompanied with depletion of FancA. In sum, our findings indicate that ganetespib strongly potentiates the antitumor efficacy of carboplatin by causing combined inhibition of DNA repair and cell cycle control mechanisms, thus triggering global chromosome disruption, aberrant mitosis and cell death."],["dc.identifier.doi","10.1038/cdd.2016.124"],["dc.identifier.isi","000395789500012"],["dc.identifier.pmid","27834954"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43281"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Nature Publishing Group"],["dc.relation.haserratum","/handle/2/73731"],["dc.relation.issn","1476-5403"],["dc.relation.issn","1350-9047"],["dc.title","Strong antitumor synergy between DNA crosslinking and HSP90 inhibition causes massive premitotic DNA fragmentation in ovarian cancer cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","International Journal of Gynecological Cancer"],["dc.bibliographiccitation.volume","23"],["dc.contributor.author","Concin, Nicole"],["dc.contributor.author","Braicu, Elena Ioana"],["dc.contributor.author","Mahner, Sven"],["dc.contributor.author","Marth, Christian"],["dc.contributor.author","Moll, U."],["dc.contributor.author","Pujade-Lauraine, Eric"],["dc.contributor.author","Ray-Coquard, Isabelle"],["dc.contributor.author","Sehouli, Jalid"],["dc.contributor.author","Vergote, Ignace"],["dc.contributor.author","Zeillinger, R."],["dc.date.accessioned","2018-11-07T09:18:46Z"],["dc.date.available","2018-11-07T09:18:46Z"],["dc.date.issued","2013"],["dc.identifier.isi","000330379501527"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/28478"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.publisher.place","Philadelphia"],["dc.title","GANNET53: AN UPCOMING CLINICAL TRIAL BASED ON A DRUG STRATEGY TARGETING STABILISED MUTANT P53 TO COMBAT PLATINUM-RESISTANT OVARIAN CANCER"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","108"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Current Opinion in Oncology"],["dc.bibliographiccitation.lastpage","113"],["dc.bibliographiccitation.volume","26"],["dc.contributor.author","Schulz, Ramona"],["dc.contributor.author","Moll, Ute M."],["dc.date.accessioned","2018-11-07T09:47:16Z"],["dc.date.available","2018-11-07T09:47:16Z"],["dc.date.issued","2014"],["dc.description.abstract","Purpose of reviewMacrophage migration inhibitory factor (MIF), originally identified as a proinflammatory cytokine, is highly elevated in many human cancer types, independent of their histological origin. MIF's tumour promoting activities correlate with tumour aggressiveness and poor clinical prognosis. Genetic depletion of MIF in mouse cancer models results in significant inhibition of cell proliferation and induction of apoptosis, making it an attractive target for anticancer therapies. Here, we summarize the current possibilities to inhibit MIF function in cancer.Recent findingsAll known small molecule MIF inhibitors antagonize MIF's enzymatic function. However, a recent knockin mouse model suggested that protein interactions play a bigger biological role in tumour cell growth regulation than MIF's enzymatic activity. Thus, alternative strategies are important for targeting MIF. Recently, we identified that MIF in cancer cells is highly stabilized through the heat shock protein 90 machinery (HSP90). Thus, MIF is an HSP90 client. Pharmacological inhibition of the Hsp90 ATPase activity results in MIF degradation in several types of cancer cells. This provides a new way to inhibit MIF function independent of its enzymatic activity.SummaryTargeting the HSP90 machinery is a promising way to inhibit MIF function in cancer. Along with MIF and dependent on the molecular make-up of the tumour, a large number of other critical tumourigenic proteins are also destabilized by HSP90 inhibition, overall resulting in a profound block of tumour growth."],["dc.identifier.doi","10.1097/CCO.0000000000000036"],["dc.identifier.isi","000327996500016"],["dc.identifier.pmid","24225413"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/35072"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","1531-703X"],["dc.relation.issn","1040-8746"],["dc.title","Targeting the heat shock protein 90: a rational way to inhibit macrophage migration inhibitory factor function in cancer"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","526"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","The FASEB Journal"],["dc.bibliographiccitation.lastpage","543"],["dc.bibliographiccitation.volume","31"],["dc.contributor.author","Brocks, Tania"],["dc.contributor.author","Fedorchenko, Oleg"],["dc.contributor.author","Schliermann, Nicola"],["dc.contributor.author","Stein, Astrid"],["dc.contributor.author","Moll, Ute M."],["dc.contributor.author","Seegobin, Seth"],["dc.contributor.author","Dewor, Manfred"],["dc.contributor.author","Hallek, Michael"],["dc.contributor.author","Marquardt, Yvonne"],["dc.contributor.author","Fietkau, Katharina"],["dc.contributor.author","Heise, Ruth"],["dc.contributor.author","Huth, Sebastian"],["dc.contributor.author","Pfister, Herbert"],["dc.contributor.author","Bernhagen, Juergen"],["dc.contributor.author","Bucala, Richard"],["dc.contributor.author","Baron,, Jens M."],["dc.contributor.author","Fingerle‐Rowson, Guenter"],["dc.date.accessioned","2020-12-10T18:19:45Z"],["dc.date.available","2020-12-10T18:19:45Z"],["dc.date.issued","2017"],["dc.description.abstract","The response of the skin to harmful environmental agents is shaped decisively by the status of the immune system. Keratinocytes constitutively express and secrete the chemokine-like mediator, macrophage migration inhibitory factor (MIF), more strongly than dermal fibroblasts, thereby creating a MIF gradient in skin. By using global and epidermis-restricted Mif-knockout (Mif(-1-) and K14-Cre(+ltg) ;Mif(fllft)) mice, we found that MIF both recruits and maintains antigen-presenting cells in the dermis/epidermis. The reduced presence of antigen-presenting cells in the absence of MIF was associated with accelerated and increased formation of nonmelanoma skin tumors during chemical carcinogenesis. Our results demonstrate that MIF is essential for maintaining innate immunity in skin. Loss of keratinocyte-derived MIF leads to a loss of control of epithelial skin tumor formation in chemical skin carcinogenesis, which highlights an unexpected tumor-suppressive activity of MIF in murine skin.- Brocks, T., Fedorchenko, O., Schliermann, N., Stein, A., Moll, U. M., Seegobin, S., Dewor, M., Hallek, M., Marquardt, Y., Fietkau, K., Heise, R., Huth, S., Pfister, H., Bernhagen, J., Bucala, R., Baron, J. M., Fingerle-Rowson, G. Macrophage migration inhibitory factor protects from nonmelanoma epidermal tumors by regulating the number of antigen-presenting cells in skin."],["dc.identifier.doi","10.1096/fj.201600860R"],["dc.identifier.eissn","1530-6860"],["dc.identifier.isi","000394235400009"],["dc.identifier.issn","0892-6638"],["dc.identifier.pmid","27825106"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/75365"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Federation Amer Soc Exp Biol"],["dc.relation.issn","1530-6860"],["dc.relation.issn","0892-6638"],["dc.title","Macrophage migration inhibitory factor protects from nonmelanoma epidermal tumors by regulating the number of antigen‐presenting cells in skin"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","398"],["dc.bibliographiccitation.issue","7578"],["dc.bibliographiccitation.journal","Nature"],["dc.bibliographiccitation.lastpage","398"],["dc.bibliographiccitation.volume","527"],["dc.contributor.author","Alexandrova, E. M."],["dc.contributor.author","Yallowitz, A. R."],["dc.contributor.author","Li, D."],["dc.contributor.author","Xu, S."],["dc.contributor.author","Schulz, R."],["dc.contributor.author","Proia, D. A."],["dc.contributor.author","Lozano, G."],["dc.contributor.author","Dobbelstein, Matthias"],["dc.contributor.author","Moll, U. M."],["dc.date.accessioned","2022-03-01T11:45:50Z"],["dc.date.available","2022-03-01T11:45:50Z"],["dc.date.issued","2015"],["dc.identifier.doi","10.1038/nature15720"],["dc.identifier.pii","BFnature15720"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103468"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.eissn","1476-4687"],["dc.relation.iserratumof","/handle/2/36569"],["dc.relation.isformatof","/handle/2/36569"],["dc.relation.issn","0028-0836"],["dc.rights.uri","http://www.springer.com/tdm"],["dc.title","Erratum: Corrigendum: Improving survival by exploiting tumour dependence on stabilized mutant p53 for treatment"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","erratum_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1776"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Cell Cycle"],["dc.bibliographiccitation.lastpage","1781"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Palacios, Gustavo"],["dc.contributor.author","Talos, Flaminia"],["dc.contributor.author","Nemajerova, Alice"],["dc.contributor.author","Moll, Ute M."],["dc.contributor.author","Petrenko, Oleksi"],["dc.date.accessioned","2018-11-07T11:13:57Z"],["dc.date.available","2018-11-07T11:13:57Z"],["dc.date.issued","2008"],["dc.description.abstract","To better understand the role of E2F1 in tumor formation, we analyzed spontaneous tumorigenesis in p53(-/-)E2F1(+/+) and p53(-/-)E2F1(-/-) mice. We show that the combined loss of p53 and E2F1 leads to an increased incidence of sarcomas and carcinomas compared to the loss of p53 alone. E2F1-deficient tumors show wide chromosomal variation, indicative of genomic instability. Consistent with this, p53(-/-)E2F1(-/-) primary fibroblasts have a reduced capacity to maintain genomic stability when exposed to S-phase inhibitors or genotoxic drugs. A major mechanism of E2F1's contribution to genomic integrity lies in mediating stabilization and engagement of the Rb protein."],["dc.description.sponsorship","NCI NIH HHS [R01 CA060664-13, R01 CA060664]"],["dc.identifier.doi","10.4161/cc.7.12.6030"],["dc.identifier.isi","000257249300013"],["dc.identifier.pmid","18583939"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/54017"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Landes Bioscience"],["dc.relation.issn","1538-4101"],["dc.title","E2F1 plays a direct role in Rb stabilization and p53-independent tumor suppression"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2584"],["dc.bibliographiccitation.issue","16"],["dc.bibliographiccitation.journal","Cell Cycle"],["dc.bibliographiccitation.lastpage","2590"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Palacios, Gustavo"],["dc.contributor.author","Crawford, Howard C."],["dc.contributor.author","Vaseva, Angelina V."],["dc.contributor.author","Moll, Ute M."],["dc.date.accessioned","2018-11-07T11:12:07Z"],["dc.date.available","2018-11-07T11:12:07Z"],["dc.date.issued","2008"],["dc.description.abstract","Classic but also novel roles of p53 are becoming increasingly well characterized. We previously showed that ex vivo retroviral transfer of mitochondrially targeted wild type p53 (mitop53) in the E mu-myc mouse lymphoma model efficiently induces tumor cell killing in vivo. In an effort to further explore the therapeutic potential of mitop53 for its pro-apoptotic effect in solid tumors, we generated replication-deficient recombinant human Adenovirus type 5 vectors. We show here that adenoviral delivery of mitop53 by intratumoral injection into HCT116 human colon carcinoma xenograft tumors in nude mice is surprisingly effective, resulting in tumor cell death of comparable potency to conventional p53. These apoptotic effects in vivo were confirmed by Ad5-mitop53 mediated cell death of HCT116 cells in culture. Together, these data provide encouragement to further explore the potential for novel mitop53 proteins in cancer therapy to execute the shortest known circuitry of p53 death signaling."],["dc.description.sponsorship","National Cancer Institute"],["dc.identifier.isi","000258829900020"],["dc.identifier.pmid","18719383"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/53589"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Landes Bioscience"],["dc.relation.issn","1538-4101"],["dc.title","Mitochondrially targeted wild-type p53 induces apoptosis in a solid human tumor xenograft model"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","352"],["dc.bibliographiccitation.issue","7560"],["dc.bibliographiccitation.journal","Nature"],["dc.bibliographiccitation.lastpage","+"],["dc.bibliographiccitation.volume","523"],["dc.contributor.author","Alexandrova, Evguenia M."],["dc.contributor.author","Yallowitz, A. R."],["dc.contributor.author","Li, D."],["dc.contributor.author","Xu, S."],["dc.contributor.author","Schulz, R."],["dc.contributor.author","Proia, D. A."],["dc.contributor.author","Lozano, G."],["dc.contributor.author","Dobbelstein, Matthias"],["dc.contributor.author","Moll, Ute M."],["dc.date.accessioned","2018-11-07T09:54:36Z"],["dc.date.available","2018-11-07T09:54:36Z"],["dc.date.issued","2015"],["dc.description.abstract","Missense mutations in p53 generate aberrant proteins with abrogated tumour suppressor functions that can also acquire oncogenic gain-of-function activities that promote malignant progression, invasion, metastasis and chemoresistance(1-5). Mutant p53 (mutp53) proteins undergo massive constitutive stabilization specifically in tumours, which is the key requisite for the acquisition of gain-of-functions activities(6-8). Although currently 11 million patients worldwide live with tumours expressing highly stabilized mutp53, it is unknown whether mutp53 is a therapeutic target in vivo. Here we use a novel mutp53 mouse model expressing an inactivatable R248Q hotspot mutation (floxQ) to show that tumours depend on sustained mutp53 expression. Upon tamoxifen-induced mutp53 ablation, allotransplanted and autochthonous tumours curb their growth, thus extending animal survival by 37%, and advanced tumours undergo apoptosis and tumour regression or stagnation. The HSP90/HDAC6 chaperone machinery, which is significantly upregulated in cancer compared with normal tissues, is a major determinant of mutp53 stabilization(9-12). We show that long-term HSP90 inhibition significantly extends the survival of mutp53 Q/- (R248Q allele(2)) and H/H (R172H allele(3)) mice by 59% and 48%, respectively, but not their corresponding p53(-/-) (also known as Trp53(-/-)) littermates. This mutp53-dependent drug effect occurs in H/H mice treated with 17DMAG+SAHA and in H/H and Q/- mice treated with the potent Hsp90 inhibitor ganetespib. Notably, drug activity correlates with induction of mutp53 degradation, tumour apoptosis and prevention of T-cell lymphomagenesis. These proof-of-principle data identify mutp53 as an actionable cancer-specific drug target."],["dc.identifier.doi","10.1038/nature14430"],["dc.identifier.isi","000357950900043"],["dc.identifier.pmid","26009011"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36569"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.haserratum","/handle/2/103468"],["dc.relation.issn","1476-4687"],["dc.relation.issn","0028-0836"],["dc.title","Improving survival by exploiting tumour dependence on stabilized mutant p53 for treatment"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]