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| 1 | Ligand stimulation of CD95 induces activation of PIk3 followed by phosphorylation of caspase-8显示文摘在有它的 ligand 的 CD95 受体的相互作用之上,适配器分子 FADD (MORT1 ) 的顺序的协会, caspases-8/10,和 caspase-8/10 管理者 c 扭动支持形式导致导致死亡的发信号建筑群的形成。这里,我们识别像马球的 kinase (Plk ) 3 死亡受体 CD95 作为一个新相互作用合伙。Plk3 的酶的活动与它的 ligand 增加 CD95 受体的后面的相互作用。大美人(击倒) 或 caspase-8, CD95 或 FADD 击倒在 CD95 刺激之上阻止 Plk3 的激活,为 Plk3 激活建议一个功能的磁盘的一个要求。而且,我们为 Plk3 作为新底层识别 caspase-8。Phosphorylation 在 T273 上发生并且导致 caspase-8 proapoptotic 功能的刺激。在在一个营救实验或在 CRISPR/Cas9 产生的 Plk3 击倒房间表示 non-phosphorylatable caspase-8-T273A 异种的房间的 CD95 的刺激减少显著地处理 caspase-8。低 T273 phosphorylation 在 95 个肛门肿瘤病人的一个队与低 Plk3 表示显著地相关。我们的数据在 Plk 家庭以内建议 kinase 激活的新奇机制并且与高 Plk3 在肿瘤为外来的死亡小径的刺激建议一个新模型表示。 | Christina Helmke Monika Raab Franz Rodel Yves Matthess Thomas Oellerich Ranadip Mandal Mourad Sanhaji Henning Urlaub Claus Rodel Sven Becker Klaus Strebhardt | 2016 | Cell Research2016，26，8： | 1 |
| 2 | Random forests as a tool for ecohydrological distribution modelling显示文摘 | Jan Peters Bernard De Baets Niko E.C. Verhoest Roeland Samson Sven Degroeve Piet De Becker Willy Huybrechts | 2007 | Ecological Modelling2007，，2： | 1 |
| 3 | SCAPE: Big Data Meets DigitalPreservation显示文摘 | Ross King Rainer Schmidt Christoph Becker Sven Schlarb | | ERCIM0，，89： | 1 |
| 4 | Static magnetic fields increase tumor microvessel leakiness and improve antitumoral efficacy in combination with paclitaxel 显示文摘 | Donata Gellrich Sven Becker Sebastian Strieth | 2014 | Cancer Letters2014，343，1： | 1 |
| 5 | Antidiabetic profiling of veramycins,polyketides accessible by biosynthesis,chemical synthesis and precursor-directed modification显示文摘Seven new polyketides,termed veramycins,were isolated from a Streptomyces sp.from the Sanofi microbial strain collection along with their known congeners NFAT-133 and TM-123.Veramycin A,anα-pyrone congener of TM-123 and NFAT-133 showed an increased baseline deoxy-glucose uptake in the absence of insulin in a modified L6 rat skeletal muscle cell line(L6 GLUT4 AS160-like cells).In addition,both compounds slightly increased the sensitivity to insulin in this cell line.Total syntheses of NFAT-133,TM-123 and veramycin A were accomplished starting from a central building block,which bears the three contiguous stereogenic centers of this polyketide family.Our approach enables an efficient,selective and flexible access to all possible isomers of the stereotriad for further exploration of this series as a potential anti-diabetic lead structure as exemplified by the synthesis of an NFAT-133 epimer.Finally,the corresponding biosynthetic gene cluster(BGC)was identified by genome sequencing and gene inactivation.Based on feeding experiments,a biosynthetic pathway was proposed,which enabled access to new veramycin A analogs by precursor-directed biosynthesis. | Denis Dardić Nils Böhringer Alberto Plaza Florian Zubeil Juliane Pohl Svenja Sommer Leo Padva Jonathan Becker Maria A.Patras Mona-Katharina Bill Michael Kurz Luigi Toti Sven W.Görgens Sören M.M.Schuler AndréBillion Oliver Schwengers Paulus Wohlfart Alexander Goesmann Norbert Tennagels Andreas Vilcinskas Peter E.Hammann Till F.Schäberle Armin Bauer | 2022 | Organic Chemistry Frontiers2022，9，6： | 1 |
| 6 | Quantitative chemical proteomics reveals a Plkl inhibitor-compromised cell death pathway in human cells显示文摘 | Monika Raab Fiona Pachl Andrea Kraemer Elisabeth Kurunci-Csacsko Christina Doetsch Rainald Knecht Sven Becker Bernhard Kuster Klaus Strebhardt | 2014 | Cell Research2014，24，9： | 0 |
| 7 | Rescue of p53 functions by in vitro-transcribed mRNA impedes the growth of high-grade serous ovarian cancer显示文摘Background:The cellular tumor protein p53(TP53)is a tumor suppressor gene that is frequently mutated in human cancers.Among various cancer types,the very aggressive high-grade serous ovarian carcinoma(HGSOC)exhibits the high-est prevalence of TP53 mutations,present in>96%of cases.Despite intensive efforts to reactivate p53,no clinical drug has been approved to rescue p53 func-tion.In this study,our primary objective was to administer in vitro-transcribed(IVT)wild-type(WT)p53-mRNA to HGSOC cell lines,primary cells,and ortho-topic mouse models,with the aim of exploring its impact on inhibiting tumor growth and dissemination,both in vitro and in vivo.Methods:To restore the activity of p53,WT p53 was exogenously expressed in HGSOC cell lines using a mammalian vector system.Moreover,IVT WT p53 mRNA was delivered into different HGSOC model systems(primary cells and patient-derived organoids)using liposomes and studied for proliferation,cell cycle progression,apoptosis,colony formation,and chromosomal instabil-ity.Transcriptomic alterations induced by p53 mRNA were analyzed using RNA sequencing in OVCAR-8 and primary HGSOC cells,followed by ingenuity path-way analysis.In vivo effects on tumor growth and metastasis were studied using orthotopic xenografts and metastatic intraperitoneal mouse models.Results:Reactivation of the TP53 tumor suppressor gene was explored in differ-ent HGSOC model systems using newly designed IVT mRNA-based methods.The introduction of WT p53 mRNA triggered dose-dependent apoptosis,cell cycle arrest,and potent long-lasting inhibition of HGSOC cell proliferation.Transcriptome analysis of OVCAR-8 cells upon mRNA-based p53 reactivation revealed significant alterations in gene expression related to p53 signaling,such as apoptosis,cell cycle regulation,and DNA damage.Restoring p53 function concurrently reduces chromosomal instability within the HGSOC cells,under-scoring its crucial contribution in safeguarding genomic integrity by moderating the baseline occurrence of double-strand breaks arising from replication stress.Furthermore,in various mouse models,treatment with p53 mRNA reduced tumor growth and inhibited tumor cell dissemination in the peritoneal cavity in a dose-dependent manner.Conclusions:The IVT mRNA-based reactivation of p53 holds promise as a potential therapeutic strategy for HGSOC,providing valuable insights into the molecular mechanisms underlying p53 function and its relevance in ovarian cancer treatment. | Monika Raab Izabela Kostova Samuel Peña-Llopis Daniela Fietz Monika Kressin Seyed Mohsen Aberoumandi Evelyn Ullrich Sven Becker Mourad Sanhaji Klaus Strebhardt | 2024 | Cancer Communications2024，44，1： | 0 |
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