Ernst Schering Foundation symposium proceedings最新文献_第2页

Approaches to discovering drugs that regulate E3 ubiquitin ligases. 发现调节E3泛素连接酶的药物的方法。

Ernst Schering Foundation symposium proceedings Pub Date : 2008-01-01 DOI: 10.1007/2789_2008_107

J Huang, L Tsvetkov, K Qu, S Daniel-Issakani, D G Payan

引用次数: 2

Inhibiting Hdm2 and ubiquitin-activating enzyme: targeting the ubiquitin conjugating system in cancer. 抑制Hdm2和泛素活化酶:靶向泛素偶联系统在癌症中的作用。

Ernst Schering Foundation symposium proceedings Pub Date : 2008-01-01 DOI: 10.1007/2789_2008_108

A M Weissman, Y Yang, J Kitagaki, C A Sasiela, J A Beutler, B R O'Keefe

{"title":"Inhibiting Hdm2 and ubiquitin-activating enzyme: targeting the ubiquitin conjugating system in cancer.","authors":"A M Weissman, Y Yang, J Kitagaki, C A Sasiela, J A Beutler, B R O'Keefe","doi":"10.1007/2789_2008_108","DOIUrl":"https://doi.org/10.1007/2789_2008_108","url":null,"abstract":"The ubiquitin conjugating system represents a rich source of potential molecular targets for cancer and other diseases. One target of great interest is the RING finger ubiquitin ligase (E3) Hdm2/Mdm2, which is frequently overexpressed in cancer and is a critical E3 for the tumor suppressor p53. For those 50% of tumors that express wild-type p53, agents that inhibit Hdm2 have great potential clinical utility. We summarize our ongoing efforts to identify inhibitors of Hdm2 E3 activity by high-throughput screening of both defined small molecules and natural product extracts. Employing a strategy using both enzymatic and cell-based assays, we have identified inhibitors that block the E3 activity of Hdm2, activate a p53 response, preferentially kill p53-expressing cells, and have the capacity to differentially cause death of transformed cells. Therefore, screening for inhibitors of Hdm2 ubiquitin ligase activity through in vitro assays represents a powerful means of identifying molecules that activate p53 in cancer cells to induce apoptosis. We also discuss the potential of inhibitors of ubiquitin-activating enzyme (E1) that were discovered during these screens. E1 inhibitors may similarly serve as the basis for novel therapeutics. Additionally, they represent unique tools for providing new insights into the ubiquitin conjugating system.","PeriodicalId":87471,"journal":{"name":"Ernst Schering Foundation symposium proceedings","volume":" 1","pages":"171-90"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/2789_2008_108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27973168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12

Ubiquitination of Myc: proteasomal degradation and beyond. Myc的泛素化:蛋白酶体降解及其他。

Ernst Schering Foundation symposium proceedings Pub Date : 2008-01-01 DOI: 10.1007/2789_2008_103

J Müller, M Eilers

引用次数: 22

Transcriptional control and the ubiquitin-proteasome system. 转录控制与泛素-蛋白酶体系统。

Ernst Schering Foundation symposium proceedings Pub Date : 2008-01-01 DOI: 10.1007/2789_2008_102

A. Leung, F. Geng, A. Daulny, G. Collins, P. Guzzardo, W. Tansey

引用次数: 16

Organocatalysis. Berlin, April 2007. Preface. Organocatalysis。柏林，2007年4月。前言。

Ernst Schering Foundation symposium proceedings Pub Date : 2007-01-01

Manfred T Reetz, Benjamin List, Stefan Jaroch, Hilmar Weinmann

引用次数: 0

Progestins and the mammary gland. From basic science to clinical applications. Preface. 孕激素和乳腺。从基础科学到临床应用。前言。

Ernst Schering Foundation symposium proceedings Pub Date : 2007-01-01

Orla M Conneely, Christiane Otto

引用次数: 0

Minimally invasive biomarkers for therapy monitoring. 用于治疗监测的微创生物标志物。

Ernst Schering Foundation symposium proceedings Pub Date : 2007-01-01 DOI: 10.1007/2789_2008_093

P McSheehy, P Allegrini, S Ametaby, M Becquet, T Ebenhan, M Honer, S Ferretti, H Lane, P Schubiger, C Schnell, M Stumm, J Wood

{"title":"Minimally invasive biomarkers for therapy monitoring.","authors":"P McSheehy, P Allegrini, S Ametaby, M Becquet, T Ebenhan, M Honer, S Ferretti, H Lane, P Schubiger, C Schnell, M Stumm, J Wood","doi":"10.1007/2789_2008_093","DOIUrl":"https://doi.org/10.1007/2789_2008_093","url":null,"abstract":"Development of new drugs and optimal application of the drugs currently in use in clinical chemotherapy requires the application of biomarkers. Ideally, these biomarkers would stratify patients so that only those patients likely to respond to a particular therapy receive that therapy. However, that is not always feasible, and an alternative is to make use of early response biomarkers to determine the responding population. In this paper, a number of generic (i.e. not necessarily specific to the action mechanism of the compound) early-response biomarkers are discussed and compared in different models and with three compounds with quite different mechanisms of action: a VEGF-R inhibitor (PTK787), an mTOR inhibitor (RAD001) and a microtubule stabiliser (EPO906). The methods include noninvasive DCE-MRI and PET imaging for measuring tumour vascularity, metabolism and proliferation, as well as the minimally invasive WIN method for measuring tumour interstitial pressure (IFP). The data show that drug-induced changes in IFP (delta IFP) involve mechanism-dependent changes in the tumour vascular architecture, and that delta IFP may be considered a universal generic early-response marker of tumour response to therapy.","PeriodicalId":87471,"journal":{"name":"Ernst Schering Foundation symposium proceedings","volume":" 4","pages":"153-88"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/2789_2008_093","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27690212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

The role of diacylglycerol kinases in T cell anergy. 二酰甘油激酶在T细胞能量中的作用。

Ernst Schering Foundation symposium proceedings Pub Date : 2007-01-01 DOI: 10.1007/2789_2007_073

X. Zhong, B. Olenchock, G. Koretzky

引用次数: 8

Systems biology of T cell activation. T细胞活化的系统生物学。

Ernst Schering Foundation symposium proceedings Pub Date : 2007-01-01

J A Lindquist, B Schraven

引用次数: 0

Solving the IRAK-4 enigma: application of kinase-dead knock-in mice. 解决IRAK-4之谜:激酶死亡敲入小鼠的应用。

Ernst Schering Foundation symposium proceedings Pub Date : 2007-01-01

M Koziczak-Holbro, C Joyce, A Glück, B Kinzel, M Müller, H Gram

{"title":"Solving the IRAK-4 enigma: application of kinase-dead knock-in mice.","authors":"M Koziczak-Holbro, C Joyce, A Glück, B Kinzel, M Müller, H Gram","doi":"","DOIUrl":"","url":null,"abstract":"Interleukin-1 receptor-associated kinase (IRAK-4) is an essential component of the signal transduction complex downstream of the interleukin (IL)-1- and Toll-like receptors. Though regarded as the first kinase in the signaling cascade, the role of IRAK-4 kinase activity versus its scaffold function has been controversial. In order to investigate the role of IRAK-4 kinase function in vivo, we generated \"knock-in\" mice where the wild-type IRAK-4 gene is replaced with a mutant gene encoding kinase-deficient IRAK-4 protein (IRAK-4 KD). IRAK-4 kinase is rendered inactive by mutating the conserved lysine residues in the ATP pocket essential for coordinating ATP. Analyses of embryonic fibroblasts and macrophages obtained from IRAK-4 KD mice demonstrated lack of cellular responsiveness to stimulation with IL-1beta or Toll-like receptor 4 (TLR4) and TLR7 agonists. IRAK-4 KD cells were severely impaired in NF-kappaB, JNK, and p38 activation in response to IL-1beta or TLR7 ligand. In addition, activation of JNK and p38 was affected in lipopolysaccharide (LPS)-stimulated IRAK-4 KD macrophages. As a consequence, IL-1 receptor/TLR4/TLR7-mediated production of cytokines and chemokines was largely absent in these cells. Additionally, microarray analysis identified IL-1beta response genes and revealed that the induction of IL-1beta-responsive mRNAs is largely ablated in IRAK-4 KD cells. In summary, our results suggest that IRAK-4 kinase activity plays a critical role in IL-1R-, TLR4-, and TLR7-mediated induction of inflammatory responses.","PeriodicalId":87471,"journal":{"name":"Ernst Schering Foundation symposium proceedings","volume":" 3","pages":"63-82"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27467384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0