Kosinsky, Robyn Laura

[["dc.bibliographiccitation.firstpage","37906"],["dc.bibliographiccitation.issue","35"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","37918"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Kosinsky, Robyn L."],["dc.contributor.author","Wegwitz, Florian"],["dc.contributor.author","Hellbach, Nicole"],["dc.contributor.author","Dobbelstein, Matthias"],["dc.contributor.author","Mansouri, Ahmed"],["dc.contributor.author","Vogel, Tanja"],["dc.contributor.author","Begus-Nahrmann, Yvonne"],["dc.contributor.author","Johnsen, Steven A."],["dc.date.accessioned","2019-07-09T11:42:03Z"],["dc.date.available","2019-07-09T11:42:03Z"],["dc.date.issued","2015-11-10"],["dc.description.abstract","Epigenetic regulatory mechanisms play a central role in controlling gene expression during development, cell differentiation and tumorigenesis. Monoubiquitination of histone H2B is one epigenetic modification which is dynamically regulated by the opposing activities of specific ubiquitin ligases and deubiquitinating enzymes (DUBs). The Ubiquitin-specific Protease 22 (USP22) is the ubiquitin hydrolase component of the human SAGA complex which deubiquitinates histone H2B during transcription. Recently, many studies have investigated an oncogenic potential of USP22 overexpression. However, its physiological function in organ maintenance, development and its cellular function remain largely unknown. A previous study reported embryonic lethality in Usp22 knockout mice. Here we describe a mouse model with a global reduction of USP22 levels which expresses the LacZ gene under the control of the endogenous Usp22 promoter. Using this reporter we found Usp22 to be ubiquitously expressed in murine embryos. Notably, adult Usp22lacZ/lacZ displayed low residual Usp22 expression levels coupled with a reduced body size and weight. Interestingly, the reduction of Usp22 significantly influenced the frequency of differentiated cells in the small intestine and the brain while H2B and H2Bub1 levels remained constant. Taken together, we provide evidence for a physiological role for USP22 in controlling cell differentiation and lineage specification."],["dc.identifier.doi","10.18632/oncotarget.5412"],["dc.identifier.pmid","26431380"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12736"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58576"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1949-2553"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.title","Usp22 deficiency impairs intestinal epithelial lineage specification in vivo."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","6334"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Nucleic Acids Research"],["dc.bibliographiccitation.lastpage","6349"],["dc.bibliographiccitation.volume","45"],["dc.contributor.author","Mishra, Vivek Kumar"],["dc.contributor.author","Wegwitz, Florian"],["dc.contributor.author","Kosinsky, Robyn Laura"],["dc.contributor.author","Sen, Madhobi"],["dc.contributor.author","Baumgartner, Roland"],["dc.contributor.author","Wulff, Tanja"],["dc.contributor.author","Siveke, Jens T."],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.contributor.author","Najafova, Zeynab"],["dc.contributor.author","Kari, Vijayalakshmi"],["dc.contributor.author","Kohlhof, Hella"],["dc.contributor.author","Hessmann, Elisabeth"],["dc.contributor.author","Johnsen, Steven A."],["dc.date.accessioned","2018-11-07T10:22:37Z"],["dc.date.available","2018-11-07T10:22:37Z"],["dc.date.issued","2017"],["dc.description.abstract","Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a particularly dismal prognosis. Histone deacetylases (HDAC) are epigenetic modulators whose activity is frequently deregulated in various cancers including PDAC. In particular, class-I HDACs (HDAC 1, 2, 3 and 8) have been shown to play an important role in PDAC. In this study, we investigated the effects of the class Ispecific HDAC inhibitor (HDACi) 4SC-202 in multiple PDAC cell lines in promoting tumor cell differentiation. We show that 4SC-202 negatively affects TGF beta signaling and inhibits TGF beta-induced epithelial-tomesenchymal transition (EMT). Moreover, 4SC-202 markedly induced p21 (CDKN1A) expression and significantly attenuated cell proliferation. Mechanistically, genome-wide studies revealed that 4SC-202-induced genes were enriched for Bromodomain-containing Protein-4 (BRD4) and MYC occupancy. BRD4, a well-characterized acetyllysine reader, has been shown to play a major role in regulating transcription of selected subsets of genes. Importantly, BRD4 and MYC are essential for the expression of a subgroup of genes induced by class-I HDACi. Taken together, our study uncovers a previously unknown role of BRD4 and MYC in eliciting the HDACi-mediated induction of a subset of genes and provides molecular insight into the mechanisms of HDACi action in PDAC."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2017"],["dc.identifier.doi","10.1093/nar/gkx212"],["dc.identifier.isi","000403693000023"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14605"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42309"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","1362-4962"],["dc.relation.issn","0305-1048"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Histone deacetylase class-I inhibition promotes epithelial gene expression in pancreatic cancer cells in a BRD4-and MYC-dependent manner"],["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.issue","12"],["dc.bibliographiccitation.journal","Cell Death & Disease"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Kosinsky, Robyn Laura"],["dc.contributor.author","Helms, Marlena"],["dc.contributor.author","Zerche, Maria"],["dc.contributor.author","Wohn, Luisa"],["dc.contributor.author","Dyas, Anna"],["dc.contributor.author","Prokakis, Evangelos"],["dc.contributor.author","Kazerouni, Zahra Basir"],["dc.contributor.author","Bedi, Upasana"],["dc.contributor.author","Wegwitz, Florian"],["dc.contributor.author","Johnsen, Steven A."],["dc.date.accessioned","2020-12-10T18:09:43Z"],["dc.date.available","2020-12-10T18:09:43Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1038/s41419-019-2141-9"],["dc.identifier.eissn","2041-4889"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17081"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/73737"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","USP22-dependent HSP90AB1 expression promotes resistance to HSP90 inhibition in mammary and colorectal cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Clinical Epigenetics"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Sen, Madhobi"],["dc.contributor.author","Wang, Xin"],["dc.contributor.author","Hamdan, Feda H."],["dc.contributor.author","Rapp, Jacobe"],["dc.contributor.author","Eggert, Jessica"],["dc.contributor.author","Kosinsky, Robyn Laura"],["dc.contributor.author","Wegwitz, Florian"],["dc.contributor.author","Kutschat, Ana Patricia"],["dc.contributor.author","Younesi, Fereshteh S."],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Grade, Marian"],["dc.contributor.author","Hessmann, Elisabeth"],["dc.contributor.author","Papantonis, Argyris"],["dc.contributor.author","Strӧbel, Philipp"],["dc.contributor.author","Johnsen, Steven A."],["dc.date.accessioned","2020-12-10T18:39:06Z"],["dc.date.available","2020-12-10T18:39:06Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1186/s13148-019-0690-5"],["dc.identifier.eissn","1868-7083"],["dc.identifier.issn","1868-7075"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16438"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/77543"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","ARID1A facilitates KRAS signaling-regulated enhancer activity in an AP1-dependent manner in colorectal cancer cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["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.artnumber","32"],["dc.bibliographiccitation.journal","Genome Biology"],["dc.bibliographiccitation.volume","18"],["dc.contributor.author","Xie, Wanhua"],["dc.contributor.author","Nagarajan, Sankari"],["dc.contributor.author","Baumgart, Simon J."],["dc.contributor.author","Kosinsky, Robyn Laura"],["dc.contributor.author","Najafova, Zeynab"],["dc.contributor.author","Kari, Vijayalakshmi"],["dc.contributor.author","Hennion, Magali"],["dc.contributor.author","Indenbirken, Daniela"],["dc.contributor.author","Bonn, Stefan"],["dc.contributor.author","Grundhoff, Adam"],["dc.contributor.author","Wegwitz, Florian"],["dc.contributor.author","Mansouri, Ahmed"],["dc.contributor.author","Johnsen, Steven A."],["dc.date.accessioned","2018-11-07T10:27:18Z"],["dc.date.available","2018-11-07T10:27:18Z"],["dc.date.issued","2017"],["dc.description.abstract","Background: Monoubiquitination of H2B (H2Bub1) is a largely enigmatic histone modification that has been linked to transcriptional elongation. Because of this association, it has been commonly assumed that H2Bub1 is an exclusively positively acting histone modification and that increased H2Bub1 occupancy correlates with increased gene expression. In contrast, depletion of the H2B ubiquitin ligases RNF20 or RNF40 alters the expression of only a subset of genes. Results: Using conditional Rnf40 knockout mouse embryo fibroblasts, we show that genes occupied by low to moderate amounts of H2Bub1 are selectively regulated in response to Rnf40 deletion, whereas genes marked by high levels of H2Bub1 are mostly unaffected by Rnf40 loss. Furthermore, we find that decreased expression of RNF40-dependent genes is highly associated with widespread narrowing of H3K4me3 peaks. H2Bub1 promotes the broadening of H3K4me3 to increase transcriptional elongation, which together lead to increased tissue- specific gene transcription. Notably, genes upregulated following Rnf40 deletion, including Foxl2, are enriched for H3K27me3, which is decreased following Rnf40 deletion due to decreased expression of the Ezh2 gene. As a consequence, increased expression of some RNF40-\"suppressed\" genes is associated with enhancer activation via FOXL2. Conclusion: Together these findings reveal the complexity and context-dependency whereby one histone modification can have divergent effects on gene transcription. Furthermore, we show that these effects are dependent upon the activity of other epigenetic regulatory proteins and histone modifications."],["dc.identifier.doi","10.1186/s13059-017-1159-5"],["dc.identifier.isi","000394828000003"],["dc.identifier.pmid","28209164"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14250"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43221"],["dc.notes.intern","Merged from goescholar"],["dc.notes.intern","In goescholar not merged with http://resolver.sub.uni-goettingen.de/purl?gs-1/14993 but duplicate"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1474-760X"],["dc.rights","CC BY 4.0"],["dc.rights.access","openAccess"],["dc.rights.holder","The Author(s)."],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","RNF40 regulates gene expression in an epigenetic context-dependent manner"],["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.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.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","1817"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Cancers"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Kosinsky, Robyn Laura"],["dc.contributor.author","Saul, Dominik"],["dc.contributor.author","Ammer-Herrmenau, Christoph"],["dc.contributor.author","Faubion, William A."],["dc.contributor.author","Neesse, Albrecht"],["dc.contributor.author","Johnsen, Steven A."],["dc.date.accessioned","2021-06-01T09:42:31Z"],["dc.date.available","2021-06-01T09:42:31Z"],["dc.date.issued","2021"],["dc.description.abstract","As a member of the 11-gene “death-from-cancer” gene expression signature, ubiquitin-specific protease 22 (USP22) has been considered an oncogene in various human malignancies, including colorectal cancer (CRC). We recently identified an unexpected tumor-suppressive function of USP22 in CRC and detected intestinal inflammation after Usp22 deletion in mice. We aimed to investigate the function of USP22 in intestinal inflammation as well as inflammation-associated CRC. We evaluated the effects of a conditional, intestine-specific knockout of Usp22 during dextran sodium sulfate (DSS)-induced colitis and in a model for inflammation-associated CRC. Mice were analyzed phenotypically and histologically. Differentially regulated genes were identified in USP22-deficient human CRC cells and the occupancy of active histone markers was determined using chromatin immunoprecipitation. The knockout of Usp22 increased inflammation-associated symptoms after DSS treatment locally and systemically. In addition, Usp22 deletion resulted in increased inflammation-associated colorectal tumor growth. Mechanistically, USP22 depletion in human CRC cells induced a profound upregulation of secreted protein acidic and rich in cysteine (SPARC) by affecting H3K27ac and H2Bub1 occupancy on the SPARC gene. The induction of SPARC was confirmed in vivo in our intestinal Usp22-deficient mice. Together, our findings uncover that USP22 controls SPARC expression and inflammation intensity in colitis and CRC."],["dc.description.sponsorship","Erich und Gertrud Roggenbuck-Stiftung"],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft"],["dc.description.sponsorship","Mildred Scheel postdoc fellowship"],["dc.identifier.doi","10.3390/cancers13081817"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85275"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.publisher","MDPI"],["dc.relation.eissn","2072-6694"],["dc.rights","https://creativecommons.org/licenses/by/4.0/"],["dc.title","USP22 Suppresses SPARC Expression in Acute Colitis and Inflammation-Associated Colorectal Cancer"],["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"]]