Kosinsky, Robyn Laura

[["dc.bibliographiccitation.firstpage","705"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Calcified Tissue International"],["dc.bibliographiccitation.lastpage","719"],["dc.bibliographiccitation.volume","102"],["dc.contributor.author","Saul, D."],["dc.contributor.author","Harlas, B."],["dc.contributor.author","Ahrabi, A."],["dc.contributor.author","Kosinsky, R. L."],["dc.contributor.author","Hoffmann, D. B."],["dc.contributor.author","Wassmann, M."],["dc.contributor.author","Wigger, R."],["dc.contributor.author","Böker, K. O."],["dc.contributor.author","Sehmisch, S."],["dc.contributor.author","Komrakova, M."],["dc.date.accessioned","2020-06-10T14:22:48Z"],["dc.date.available","2020-06-10T14:22:48Z"],["dc.date.issued","2017"],["dc.description.abstract","Osteoporosis is often accompanied by sarcopenia. The effect of strontium ranelate (SR) on muscle tissue has not been investigated sufficiently. In this study, the effect of different SR treatments on muscle was studied. Additionally, the lumbar vertebrae were analyzed. Three-month-old female rats were divided into five groups (n = 12): Group 1: untreated (NON-OVX); Group 2: ovariectomized and left untreated (OVX); Group 3: SR after OVX until the study ended (13 weeks, SR prophylaxis and therapy = pr+th); Group 4: OVX and SR for 8 weeks (SR prophylaxis = pr); Group 5: SR for 5 weeks from the 8 week after OVX (SR therapy = SR th). SR was applied in food (630 mg/kg body weight). The size of muscle fibers, capillary density, metabolic enzymes, and mRNA expression were assessed in soleus, gastrocnemius, and longissimus muscles. The vertebral bodies underwent micro-CT, biomechanical, and ashing analyses. In general, SR did not alter the muscle histological parameters. The changes in fiber size and capillary ratio were related to the body weight. Myostatin mRNA was decreased in Sr pr+th; protein expression was not changed. SR th led to increase in mRNA expression of vascular endothelial growth factor (Vegf-B). In lumbar spine, SR pr+th enhanced biomechanical properties, bone mineral density, trabecular area, density, and thickness and cortical density. The reduced calcium/phosphate ratio in the SR pr+th group indicates the replacement of calcium by strontium ions. SR has no adverse effects on muscle tissue and it shows a favorable time-dependent effect on vertebrae. A functional analysis of muscles could verify these findings."],["dc.identifier.doi","10.1007/s00223-017-0374-0"],["dc.identifier.pmid","29242963"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/66222"],["dc.language.iso","en"],["dc.relation.eissn","1432-0827"],["dc.relation.issn","0171-967X"],["dc.title","Effect of Strontium Ranelate on the Muscle and Vertebrae of Ovariectomized Rats"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Saul, Dominik"],["dc.contributor.author","Kosinsky, Robyn Laura"],["dc.contributor.author","Atkinson, Elizabeth J."],["dc.contributor.author","Doolittle, Madison L."],["dc.contributor.author","Zhang, Xu"],["dc.contributor.author","LeBrasseur, Nathan K."],["dc.contributor.author","Pignolo, Robert J."],["dc.contributor.author","Robbins, Paul D."],["dc.contributor.author","Niedernhofer, Laura J."],["dc.contributor.author","Ikeno, Yuji"],["dc.contributor.author","Khosla, Sundeep"],["dc.date.accessioned","2022-09-01T09:50:03Z"],["dc.date.available","2022-09-01T09:50:03Z"],["dc.date.issued","2022"],["dc.description.abstract","Abstract\n Although cellular senescence drives multiple age-related co-morbidities through the senescence-associated secretory phenotype, in vivo senescent cell identification remains challenging. Here, we generate a gene set (SenMayo) and validate its enrichment in bone biopsies from two aged human cohorts. We further demonstrate reductions in SenMayo in bone following genetic clearance of senescent cells in mice and in adipose tissue from humans following pharmacological senescent cell clearance. We next use SenMayo to identify senescent hematopoietic or mesenchymal cells at the single cell level from human and murine bone marrow/bone scRNA-seq data. Thus, SenMayo identifies senescent cells across tissues and species with high fidelity. Using this senescence panel, we are able to characterize senescent cells at the single cell level and identify key intercellular signaling pathways. SenMayo also represents a potentially clinically applicable panel for monitoring senescent cell burden with aging and other conditions as well as in studies of senolytic drugs."],["dc.description.sponsorship"," Dr. Mildred Scheel Stiftung für Krebsforschung https://doi.org/10.13039/501100005973"],["dc.description.sponsorship"," Foundation for the National Institutes of Health https://doi.org/10.13039/100000009"],["dc.identifier.doi","10.1038/s41467-022-32552-1"],["dc.identifier.pii","32552"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113610"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-597"],["dc.relation.eissn","2041-1723"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Cell Death and Differentiation"],["dc.contributor.author","Kosinsky, Robyn Laura"],["dc.contributor.author","Zerche, Maria"],["dc.contributor.author","Kutschat, Ana Patricia"],["dc.contributor.author","Nair, Asha"],["dc.contributor.author","Ye, Zhenqing"],["dc.contributor.author","Saul, Dominik"],["dc.contributor.author","von Heesen, Maximilian"],["dc.contributor.author","Friton, Jessica J."],["dc.contributor.author","Schwarzer, Ana Carolina"],["dc.contributor.author","Johnsen, Steven A."],["dc.date.accessioned","2021-07-05T15:00:28Z"],["dc.date.available","2021-07-05T15:00:28Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract Despite the identification of several genetic factors linked to increased susceptibility to inflammatory bowel disease (IBD), underlying molecular mechanisms remain to be elucidated in detail. The ubiquitin ligases RNF20 and RNF40 mediate the monoubiquitination of histone H2B at lysine 120 (H2Bub1) and were shown to play context-dependent roles in the development of inflammation. Here, we aimed to examine the function of the RNF20/RNF40/H2Bub1 axis in intestinal inflammation in IBD patients and mouse models. For this purpose, intestinal sections from IBD patients were immunohistochemically stained for H2Bub1. Rnf20 or Rnf40 were conditionally deleted in the mouse intestine and mice were monitored for inflammation-associated symptoms. Using mRNA-seq and chromatin immunoprecipitation (ChIP)-seq, we analyzed underlying molecular pathways in primary intestinal epithelial cells (IECs) isolated from these animals and confirmed these findings in IBD resection specimens using ChIP-seq.The majority (80%) of IBD patients displayed a loss of H2Bub1 levels in inflamed areas and the intestine-specific deletion of Rnf20 or Rnf40 resulted in spontaneous colorectal inflammation in mice. Consistently, deletion of Rnf20 or Rnf40 promoted IBD-associated gene expression programs, including deregulation of various IBD risk genes in these animals. Further analysis of murine IECs revealed that H3K4me3 occupancy and transcription of the Vitamin D Receptor ( Vdr ) gene and VDR target genes is RNF20/40-dependent. Finally, these effects were confirmed in a subgroup of Crohn’s disease patients which displayed epigenetic and expression changes in RNF20/40-dependent gene signatures. Our findings reveal that loss of H2B monoubiquitination promotes intestinal inflammation via decreased VDR activity thereby identifying RNF20 and RNF40 as critical regulators of IBD."],["dc.description.abstract","Abstract Despite the identification of several genetic factors linked to increased susceptibility to inflammatory bowel disease (IBD), underlying molecular mechanisms remain to be elucidated in detail. The ubiquitin ligases RNF20 and RNF40 mediate the monoubiquitination of histone H2B at lysine 120 (H2Bub1) and were shown to play context-dependent roles in the development of inflammation. Here, we aimed to examine the function of the RNF20/RNF40/H2Bub1 axis in intestinal inflammation in IBD patients and mouse models. For this purpose, intestinal sections from IBD patients were immunohistochemically stained for H2Bub1. Rnf20 or Rnf40 were conditionally deleted in the mouse intestine and mice were monitored for inflammation-associated symptoms. Using mRNA-seq and chromatin immunoprecipitation (ChIP)-seq, we analyzed underlying molecular pathways in primary intestinal epithelial cells (IECs) isolated from these animals and confirmed these findings in IBD resection specimens using ChIP-seq.The majority (80%) of IBD patients displayed a loss of H2Bub1 levels in inflamed areas and the intestine-specific deletion of Rnf20 or Rnf40 resulted in spontaneous colorectal inflammation in mice. Consistently, deletion of Rnf20 or Rnf40 promoted IBD-associated gene expression programs, including deregulation of various IBD risk genes in these animals. Further analysis of murine IECs revealed that H3K4me3 occupancy and transcription of the Vitamin D Receptor ( Vdr ) gene and VDR target genes is RNF20/40-dependent. Finally, these effects were confirmed in a subgroup of Crohn’s disease patients which displayed epigenetic and expression changes in RNF20/40-dependent gene signatures. Our findings reveal that loss of H2B monoubiquitination promotes intestinal inflammation via decreased VDR activity thereby identifying RNF20 and RNF40 as critical regulators of IBD."],["dc.identifier.doi","10.1038/s41418-021-00808-w"],["dc.identifier.pii","808"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/87834"],["dc.language.iso","en"],["dc.notes.intern","DOI Import DOI-Import GROB-441"],["dc.relation.eissn","1476-5403"],["dc.relation.issn","1350-9047"],["dc.title","RNF20 and RNF40 regulate vitamin D receptor-dependent signaling in inflammatory bowel disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Oncogene"],["dc.contributor.author","Prokakis, Evangelos"],["dc.contributor.author","Dyas, Anna"],["dc.contributor.author","Grün, Regina"],["dc.contributor.author","Fritzsche, Sonja"],["dc.contributor.author","Bedi, Upasana"],["dc.contributor.author","Kazerouni, Zahra B."],["dc.contributor.author","Kosinsky, Robyn L."],["dc.contributor.author","Johnsen, Steven A."],["dc.contributor.author","Wegwitz, Florian"],["dc.date.accessioned","2021-06-01T09:41:38Z"],["dc.date.available","2021-06-01T09:41:38Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract The Ubiquitin-Specific Protease 22 (USP22) is a deubiquitinating subunit of the mammalian SAGA transcriptional co-activating complex. USP22 was identified as a member of the so-called “death-from-cancer” signature predicting therapy failure in cancer patients. However, the importance and functional role of USP22 in different types and subtypes of cancer remain largely unknown. In the present study, we leveraged human cell lines and genetic mouse models to investigate the role of USP22 in HER2-driven breast cancer (HER2 + -BC) and demonstrate for the first time that USP22 is required for the tumorigenic properties in murine and human HER2 + -BC models. To get insight into the underlying mechanisms, we performed transcriptome-wide gene expression analyses and identified the Unfolded Protein Response (UPR) as a pathway deregulated upon USP22 loss. The UPR is normally induced upon extrinsic or intrinsic stresses that can promote cell survival and recovery if shortly activated or programmed cell death if activated for an extended period. Strikingly, we found that USP22 actively suppresses UPR induction in HER2 + -BC cells by stabilizing the major endoplasmic reticulum (ER) chaperone HSPA5. Consistently, loss of USP22 renders tumor cells more sensitive to apoptosis and significantly increases the efficiency of therapies targeting the ER folding capacity. Together, our data suggest that therapeutic strategies targeting USP22 activity may sensitize tumor cells to UPR induction and could provide a novel, effective approach to treat HER2 + -BC."],["dc.identifier.doi","10.1038/s41388-021-01814-5"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/84989"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation.eissn","1476-5594"],["dc.relation.issn","0950-9232"],["dc.title","USP22 promotes HER2-driven mammary carcinoma aggressiveness by suppressing the unfolded protein response"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","izz127"],["dc.bibliographiccitation.firstpage","56"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Inflammatory Bowel Diseases"],["dc.bibliographiccitation.lastpage","65"],["dc.bibliographiccitation.volume","26"],["dc.contributor.author","Saul, Dominik"],["dc.contributor.author","Kosinsky, Robyn Laura"],["dc.date.accessioned","2019-07-31T10:24:19Z"],["dc.date.accessioned","2020-06-10T14:46:29Z"],["dc.date.available","2019-07-31T10:24:19Z"],["dc.date.available","2020-06-10T14:46:29Z"],["dc.date.issued","2019"],["dc.description.abstract","Recent studies implicate that 42% of inflammatory bowel disease (IBD) patients suffer from sarcopenia, the loss of muscle mass and strength, increasing the risk of falls and fall-related injuries. To determine the impact and molecular basis of IBD-associated sarcopenia, we sought to establish and characterize an experimental model for IBD-associated sarcopenia in vivo."],["dc.identifier.doi","10.1093/ibd/izz127"],["dc.identifier.pmid","31228348"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/66225"],["dc.language.iso","en"],["dc.relation.eissn","1536-4844"],["dc.relation.issn","1078-0998"],["dc.title","Dextran Sodium Sulfate-induced Colitis as a Model for Sarcopenia in Mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","362"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Crohn's and Colitis"],["dc.bibliographiccitation.lastpage","373"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Kosinsky, Robyn Laura"],["dc.contributor.author","Chua, Robert Lorenz"],["dc.contributor.author","Qui, Martin"],["dc.contributor.author","Saul, Dominik"],["dc.contributor.author","Mehlich, Dawid"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.contributor.author","Wegwitz, Florian"],["dc.contributor.author","Faubion, William A."],["dc.contributor.author","Johnsen, Steven A."],["dc.date.accessioned","2020-06-09T07:16:37Z"],["dc.date.available","2020-06-09T07:16:37Z"],["dc.date.issued","2019"],["dc.description.abstract","Background and aims: Inflammatory bowel diseases are linked to an increased risk of developing colorectal cancer [CRC]. Previous studies suggested that the H2B ubiquitin ligase RING finger protein-20 [RNF20] inhibited inflammatory signaling mediated by the nuclear factor kappa-light-chain-enhancer of activated B cells [NF-κB]. However, the role of RNF40, the obligate heterodimeric partner of RNF20, in the context of inflammation and CRC has not been addressed. Here, we examined the effect of RNF40 loss on CRC cells in vitro and on inflammation and inflammatory signaling in vitro and in vivo. Methods: We evaluated H2Bub1 levels in human and murine colorectal tumors by immunohistochemistry. Moreover, we correlated H2Bub1 and RNF40 levels in vivo and assessed the consequences of RNF40 depletion on cellular phenotype and gene expression in CRC cells in vitro. Finally, we examined the effect of a colon-specific loss of Rnf40 in a murine model of colitis, and assessed both local and systemic inflammation-associated consequences. Results: In vitro studies revealed that the tumorigenic phenotype of CRC cells decreased after RNF40 depletion and displayed gene expression changes related to chromosome segregation and DNA replication, as well as decreased induction of several NF-κB-associated cytokines. This effect was associated with decreased nuclear localization of NF-κB following tumor necrosis factor alpha treatment. Consistently, the colon-specific loss of Rnf40 exerted a protective local, as well as systemic, effect following acute colitis. Conclusions: Our findings suggest that RNF40 plays a central role in the maintenance of tumorigenic features and inflammatory signaling by promoting nuclear NF-κB activity."],["dc.identifier.doi","10.1093/ecco-jcc/jjy165"],["dc.identifier.isi","WOS:000464942000013"],["dc.identifier.pmid","30321325"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/66214"],["dc.identifier.url","https://publons.com/publon/28102253/"],["dc.language.iso","en"],["dc.publisher","Oxford University Press ({OUP})"],["dc.relation.issn","1873-9946"],["dc.title","Loss of RNF40 Decreases NF-B Activity in Colorectal Cancer Cells and Reduces Colitis Burden in Mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","700"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Cell Death and Differentiation"],["dc.bibliographiccitation.lastpage","714"],["dc.bibliographiccitation.volume","28"],["dc.contributor.author","Najafova, Zeynab"],["dc.contributor.author","Liu, Peng"],["dc.contributor.author","Wegwitz, Florian"],["dc.contributor.author","Ahmad, Mubashir"],["dc.contributor.author","Tamon, Liezel"],["dc.contributor.author","Kosinsky, Robyn Laura"],["dc.contributor.author","Xie, Wanhua"],["dc.contributor.author","Johnsen, Steven A."],["dc.contributor.author","Tuckermann, Jan"],["dc.date.accessioned","2021-04-14T08:23:13Z"],["dc.date.available","2021-04-14T08:23:13Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1038/s41418-020-00614-w"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/80832"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1476-5403"],["dc.relation.issn","1350-9047"],["dc.title","RNF40 exerts stage-dependent functions in differentiating osteoblasts and is essential for bone cell crosstalk"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2386"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Inflammatory Bowel Diseases"],["dc.bibliographiccitation.lastpage","2393"],["dc.bibliographiccitation.volume","24"],["dc.contributor.author","Saul, Dominik"],["dc.contributor.author","Schilling, Arndt F."],["dc.contributor.author","Kosinsky, Robyn Laura"],["dc.date.accessioned","2020-06-15T13:47:55Z"],["dc.date.available","2020-06-15T13:47:55Z"],["dc.date.issued","2018"],["dc.description.abstract","Background Colorectal cancer (CRC) is a major cause of cancer-related deaths, and tumor-related comorbidities additionally lower life quality and survival. Mutations in the tumor suppressor adenomatous polyposis coli (APC) are associated with sporadic CRC and familial adenomatous polyposis (FAP), which results in the growth of multiple intestinal cancer lesions. In some cases, inflammatory bowel diseases (IBDs) are additionally observed in CRC patients. Although APC mutations have been shown to increase bone mineral density (BMD), inflammation is associated with reduced BMD and an elevated fracture risk in IBD patients. Methods To determine the consequences of APC-driven intestinal tumorigenesis and additional inflammation on bone parameters, we utilized an APC1638N/+ mouse model. We treated 1 cohort of APC wild-type and mutant animals with dextran sodium sulfate (DSS) to induce colorectal inflammation. All mice were killed at the same age and stratified according to their tumor burden. Results As expected, a heterozygous APC mutation increased intestinal tumor numbers and the cortical BMD. This effect on bone was abrogated in mice with high intestinal tumor numbers. Moreover, we found that high tumor burden elevated bone fragility in APC-mutated mice. After DSS treatment, there were no significant changes in bone parameters of control mice. In contrast, in combination with inflammation, bone biomechanical properties severely deteriorated at high tumor burdens in APC1638N/+ animals. Conclusions Together, not only were bone parameters affected by APC status and inflammation, but also high intestinal tumor numbers, especially when combined with inflammation, were associated with an osteoporotic phenotype."],["dc.identifier.doi","10.1093/ibd/izy234"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/66262"],["dc.language.iso","en"],["dc.relation.issn","1078-0998"],["dc.title","Intestinal Inflammation and Tumor Burden as Determinants for Bone Fragility in APC-Driven Tumorigenesis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","134"],["dc.bibliographiccitation.journal","Bone"],["dc.bibliographiccitation.lastpage","144"],["dc.bibliographiccitation.volume","101"],["dc.contributor.author","Saul, D."],["dc.contributor.author","Gleitz, S."],["dc.contributor.author","Nguyen, H. H."],["dc.contributor.author","Kosinsky, R. L."],["dc.contributor.author","Sehmisch, S."],["dc.contributor.author","Hoffmann, D. B."],["dc.contributor.author","Wassmann, M."],["dc.contributor.author","Menger, B."],["dc.contributor.author","Komrakova, M."],["dc.date.accessioned","2018-11-07T10:21:53Z"],["dc.date.accessioned","2020-06-15T07:16:22Z"],["dc.date.available","2018-11-07T10:21:53Z"],["dc.date.available","2020-06-15T07:16:22Z"],["dc.date.issued","2017"],["dc.description.abstract","Osteoporosis is one of the most common diseases worldwide. In osteoporosis, vertebral fractures represent a major burden. Lipoxygenase (LOX) inhibitors such as baicalein and zileuton may represent a promising therapeutic option owing to their antioxidative effects and suppression of various inflammatory processes in muscle and bone. The effect of these LOX inhibitors on the spine was studied in osteopenic rats. Female Sprague-Dawley rats were divided two times into five groups: four groups each were ovariectomized (OVX) and one control group was non-ovariectomized (NON-OVX). Eight weeks after ovariectomy, three concentrations of baicalein (1 mg/kg body weight [BW], 10 mg/kg BW, and 100 mg/kg BW) were administered subcutaneously daily in three OVX groups for 4 weeks. Similarly, zileuton was administered in three concentrations via food for 5 weeks. In vivo computed tomography (pQCT) of the spine was performed before the treatments and at the end of the experiment. Lumbar vertebrae were subjected to a compression test, micro-CT, and ashing analyses. After baicalein treatment, cortical bone mineral density (BMD) was improved; trabecular connectivity and trabecular BMD were diminished at high dose. After zileuton treatment the total BMD, anorganic weight, trabecular nodes, and trabecular area were improved. The in vivo stress-strain index was increased and alkaline phosphatase activity in serum was enhanced after both treatments. A dose-dependent effect was not clearly observed after both treatments. The treatments using baicalein for 4 and zileuton for 5 weeks were not sufficient to change the biomechanical properties and bone volume fraction (BV/TV). Overall, baicalein improved the cortical bone parameters whereas zileuton had a favorable effect on the trabecular structure. Moreover, both treatments increased the bone formation rate. Longer trials, a combination of both LOX inhibitors, and their effect at the cellular and molecular levels should be investigated in further studies. (C) 2017 Elsevier Inc. All rights reserved."],["dc.description.sponsorship","Elsbeth Bonhoff Stiftung [N114]"],["dc.identifier.doi","10.1016/j.bone.2017.04.011"],["dc.identifier.isi","000404319300017"],["dc.identifier.pmid","28455215"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42182"],["dc.language.iso","en"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","8756-3282"],["dc.relation.issn","1873-2763"],["dc.title","Effect of the lipoxygenase-inhibitors baicalein and zileuton on the vertebra in ovariectomized rats"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1328"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Cell Death and Differentiation"],["dc.bibliographiccitation.lastpage","1340"],["dc.bibliographiccitation.volume","27"],["dc.contributor.author","Kosinsky, Robyn Laura"],["dc.contributor.author","Zerche, Maria"],["dc.contributor.author","Saul, Dominik"],["dc.contributor.author","Wohn, Luisa"],["dc.contributor.author","Wegwitz, Florian"],["dc.contributor.author","Begus-Nahrmann, Yvonne"],["dc.contributor.author","Johnsen, Steven A."],["dc.date.accessioned","2020-06-09T06:18:54Z"],["dc.date.available","2020-06-09T06:18:54Z"],["dc.date.issued","2019"],["dc.description.abstract","USP22, the deubiquitinating subunit of the SAGA transcriptional cofactor complex, is a member of an 11-gene \"death-from-cancer\" signature. USP22 has been considered an attractive therapeutic target since high levels of its expression were associated with distant metastasis, poor survival, and high recurrence rates in a wide variety of solid tumors, including colorectal cancer (CRC). We sought to investigate the role of Usp22 during tumorigenesis in vivo using a mouse model for intestinal carcinogenesis with a tissue-specific Usp22 ablation. In addition, we assessed the effects of USP22 depletion in human CRC cells on tumorigenic potential and identified underlying molecular mechanisms. For the first time, we report that USP22 has an unexpected tumor-suppressive function in vivo. Intriguingly, intestine-specific Usp22 deletion exacerbated the tumor phenotype caused by Apc mutation, resulting in significantly decreased survival and higher intestinal tumor incidence. Accordingly, human CRC cells showed increased tumorigenic properties upon USP22 reduction in vitro and in vivo and induced gene expression signatures associated with an unfavorable outcome in CRC patients. Notably, USP22 loss resulted in increased mTOR activity with the tumorigenic properties elicited by the loss of USP22 being reversible by mTOR inhibitor treatment in vitro and in vivo. Here, we demonstrate that USP22 can exert tumor-suppressive functions in CRC where its loss increases CRC burden by modulating mTOR activity. Importantly, our data uncover a tumor- and context-specific role of USP22, suggesting that USP22 expression could serve as a marker for therapeutic stratification of cancer patients."],["dc.identifier.doi","10.1038/s41418-019-0420-8"],["dc.identifier.pmid","31527800"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/66201"],["dc.language.iso","en"],["dc.relation.eissn","1476-5403"],["dc.relation.issn","1350-9047"],["dc.title","USP22 exerts tumor-suppressive functions in colorectal cancer by decreasing mTOR activity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]