Staab, Julia F.

[["dc.bibliographiccitation.artnumber","23"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","BMC Molecular and Cell Biology"],["dc.bibliographiccitation.volume","23"],["dc.contributor.author","Behrendsen, Lena Sophie"],["dc.contributor.author","Menon, Priyanka Rajeev"],["dc.contributor.author","Khan, Muhammad Jawad"],["dc.contributor.author","Gregus, Anke"],["dc.contributor.author","Wirths, Oliver"],["dc.contributor.author","Meyer, Thomas"],["dc.contributor.author","Staab, Julia"],["dc.date.accessioned","2022-07-01T07:35:21Z"],["dc.date.available","2022-07-01T07:35:21Z"],["dc.date.issued","2022"],["dc.date.updated","2022-07-25T11:18:51Z"],["dc.description.abstract","Background Signal transducer and activator of transcription 3 (STAT3) is an oncogenic transcription factor that promotes cell proliferation and immunomodulation in untransformed cells and maintains stemness of transformed cells, facilitating invasion and metastasis. Numerous point mutations in the STAT3 protein have been identified that drive malignancy in various tumor entities. The missense mutation D427H localized in the STAT3 DNA-binding domain has been previously reported in patients with NK/T cell lymphomas. To assess the biological activity of this missense mutation, we compared the STAT3-D427H mutant to wild-type (WT) protein as well as the known hyper-active mutant F174A. Results Although previously reported as an activating mutation, the STAT3-D427H mutant neither showed elevated cytokine-induced tyrosine phosphorylation nor altered nuclear accumulation, as compared to the WT protein. However, the D427H mutant displayed enhanced binding to STAT-specific DNA-binding sites but a reduced sequence specificity and dissociation rate from DNA, which was demonstrated by electrophoretic mobility shift assays. This observation is consistent with the phenotype of the homologous E421K mutation in the STAT1 protein, which also displayed enhanced binding to DNA but lacked a corresponding increase in transcriptional activity. Conclusions Based on our data, it is unlikely that the D427H missense mutation in the STAT3 protein possesses an oncogenic potential beyond the WT molecule."],["dc.description.sponsorship"," Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659"],["dc.description.sponsorship"," Georg-August-Universität Göttingen 501100003385"],["dc.description.sponsorship","Open-Access-Publikationsfonds 2022"],["dc.identifier.citation","BMC Molecular and Cell Biology. 2022 Jun 25;23(1):23"],["dc.identifier.doi","10.1186/s12860-022-00422-9"],["dc.identifier.pii","422"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112146"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-581"],["dc.relation.eissn","2661-8850"],["dc.rights","CC BY 4.0"],["dc.rights.holder","The Author(s)"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject","Lymphoma-associated missense mutation"],["dc.subject","Signal transducer and activator of transcription 3 (STAT3)"],["dc.subject","Interleukin-6 signaling"],["dc.subject","DNA binding"],["dc.subject","Gene expression"],["dc.title","Evaluation of the putative lymphoma-associated point mutation D427H in the STAT3 transcription factor"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","S0167488921001725"],["dc.bibliographiccitation.firstpage","119118"],["dc.bibliographiccitation.journal","Biochimica et Biophysica Acta. Molecular Cell Research"],["dc.contributor.author","Menon, Priyanka Rajeev"],["dc.contributor.author","Doudin, Asmma"],["dc.contributor.author","Gregus, Anke"],["dc.contributor.author","Wirths, Oliver"],["dc.contributor.author","Staab, Julia"],["dc.contributor.author","Meyer, Thomas"],["dc.date.accessioned","2021-09-01T06:42:55Z"],["dc.date.available","2021-09-01T06:42:55Z"],["dc.date.issued","2021"],["dc.identifier.doi","10.1016/j.bbamcr.2021.119118"],["dc.identifier.pii","S0167488921001725"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/89177"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-455"],["dc.relation.issn","0167-4889"],["dc.title","The anti-parallel dimer binding interface in STAT3 transcription factor is required for the inactivation of cytokine-mediated signal transduction"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","42"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Cell Communication and Signaling"],["dc.bibliographiccitation.volume","20"],["dc.contributor.author","Menon, Priyanka R."],["dc.contributor.author","Staab, Julia"],["dc.contributor.author","Gregus, Anke"],["dc.contributor.author","Wirths, Oliver"],["dc.contributor.author","Meyer, Thomas"],["dc.date.accessioned","2022-05-02T08:09:26Z"],["dc.date.accessioned","2022-08-18T12:36:44Z"],["dc.date.available","2022-05-02T08:09:26Z"],["dc.date.available","2022-08-18T12:36:44Z"],["dc.date.issued","2022-03-31"],["dc.date.updated","2022-07-29T12:17:28Z"],["dc.description.abstract","Background\r\nUnphosphorylated signal transducer and activator of transcription 1 (U-STAT1) has been reported to elicit a distinct gene expression profile as compared to tyrosine-phosphorylated STAT1 (P-STAT1) homodimers. However, the impact of U-STAT1 on the IFNγ-induced immune response mediated by P-STAT1 is unknown. By generating a double mutant of STAT1 with mutation R602L in the Src-homology 2 (SH2) domain and Y701F in the carboxy-terminal transactivation domain mimicking U-STAT1, we investigated the effects of U-STAT1 on P-STAT1-mediated signal transduction.\r\n\r\nResults\r\nIn this study, we discovered a novel activity of U-STAT1 that alters the nucleo-cytoplasmic distribution of cytokine-stimulated P-STAT1. While the dimerization-deficient mutant R602L/Y701F was not able to display cytokine-induced nuclear accumulation, it inhibited the nuclear accumulation of co-expressed IFNγ-stimulated wild-type P-STAT1. Disruption of the anti-parallel dimer interface in the R602L/Y701F mutant via additional R274W and T385A mutations did not rescue the impaired nuclear accumulation of co-expressed P-STAT1. The mutant U-STAT1 affected neither the binding of co-expressed P-STAT1 to gamma-activated sites in vitro, nor the transcription of reporter constructs and the activation of STAT1 target genes. However, the nuclear accumulation of P-STAT1 was diminished in the presence of mutant U-STAT1, which was not restored by mutations reducing the DNA affinity of mutant U-STAT1. Whereas single mutations in the amino-terminus of dimerization-deficient U-STAT1 similarly inhibited the nuclear accumulation of co-expressed P-STAT1, a complete deletion of the amino-terminus restored cytokine-stimulated nuclear accumulation of P-STAT1. Likewise, the disruption of a dimer-specific nuclear localization signal also rescued the U-STAT1-mediated inhibition of P-STAT1 nuclear accumulation.\r\n\r\nConclusion\r\nOur data demonstrate a novel role of U-STAT1 in affecting nuclear accumulation of P-STAT1, such that a high intracellular concentration of U-STAT1 inhibits the detection of nuclear P-STAT1 in immunofluorescence assays. These observations hint at a possible physiological function of U-STAT1 in buffering the nuclear import of P-STAT1, while preserving IFNγ-induced gene expression. Based on these results, we propose a model of a hypothetical import structure, the assembly of which is impaired under high concentrations of U-STAT1. This mechanism maintains high levels of cytoplasmic STAT1, while simultaneously retaining signal transduction by IFNγ."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2022"],["dc.identifier.citation","Cell Communication and Signaling. 2022 Mar 31;20(1):42"],["dc.identifier.doi","10.1186/s12964-022-00841-3"],["dc.identifier.pii","841"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/107378"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112955"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-561"],["dc.publisher","BioMed Central"],["dc.relation.eissn","1478-811X"],["dc.rights","CC BY 4.0"],["dc.rights.holder","The Author(s)"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject","STAT1"],["dc.subject","JAK-STAT signalling"],["dc.subject","Dimerization"],["dc.subject","Nuclear accumulation"],["dc.subject","Interferon-induced gene expression"],["dc.title","An inhibitory effect on the nuclear accumulation of phospho-STAT1 by its unphosphorylated form"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]