رسالة جامعية
Charakterisierung der Rolle von ETO und AML1/ETO als SHARP interagierende Proteine bei der RBP-Jkappa/SHARP vermittelten Transkriptionskontrolle von Notch-Zielgenen
| العنوان: | Charakterisierung der Rolle von ETO und AML1/ETO als SHARP interagierende Proteine bei der RBP-Jkappa/SHARP vermittelten Transkriptionskontrolle von Notch-Zielgenen |
|---|---|
| المؤلفون: | Salat, Daniela |
| بيانات النشر: | Universität Ulm |
| سنة النشر: | 2016 |
| المجموعة: | OPARU (OPen Access Repository of Ulm University) |
| مصطلحات موضوعية: | AML1/ETO, ETO, Repressorkomplex, Transkriptionskontrolle, DDC 570 / Life sciences, Gen notch |
| الوصف: | The transmembrane receptor Notch plays an important role during many developmental and differentiation processes. Ligand binding induces a proteolytic cleavage of the intracellular domain (IC) of the Notch receptor. The released IC translocates to the nucleus and associates with the DNA-binding protein RBP-J?. This leads to the recruitment of further coactivators and to the transcriptional activation of notch target genes. In the absence of IC RBP-J? represses transcription through the recruitment of corepressor complexes. SHARP has been identified as a part of aa RBP-J? repressor complex. SHARP directly interacts with RBP-J? and recruits HDACs and HDAC associated proteins to RBP-J&. This study is about the characterisation of new RBP-J?/SHARP associated proteins. The corepressor ETO was found as a SHARP interacting protein in a yeast-two-hybrid-screen. Further experiments identified other members of the ETO-family, the murine ETO-2 and Xenopus laevis ETO (xl), as SHARP interacting proteins. The chromosomal translocation t(8;21) is typical for the human acute myeloid leukaemia (FAB M2). It leads to the generation of the aberrant fusion protein AML1/ETO. ETO and AML1/ETO directly interact with SHARP through NHR1 and NHR2 as shown by GST-pull-down assays and immunoprecipitation experiments. Purification of endogenous RBP-J? complexes by DNA affinity chromatography showed that ETO and AML1/ETO are part of these complexes. In contrast to AML1/ETO ETO enhances HDAC-dependently the SHARP dependent transcriptional repression of Notch target genes. Regarding the results of this work it can be suggested that (A) ETO is a new component of the RBP-J?/SHARP repressor complex and (B) AML1/ETO in contrast to ETO leads to the activation or derepression of Notch target genes. According to this it has been shown for the first time that AML1/ETO is directly involved in the deregulation of Notch target genes. This deregulating effect of AML1/ETO may contribute to the onset of AML. |
| نوع الوثيقة: | doctoral or postdoctoral thesis |
| وصف الملف: | application/pdf |
| اللغة: | German |
| العلاقة: | https://doi.org/10.1128/MCB.01966-07Test; http://dx.doi.org/10.18725/OPARU-1154Test; https://oparu.uni-ulm.de/xmlui/123456789/1181Test; http://nbn-resolving.de/urn:nbn:de:bsz:289-vts-65481Test |
| DOI: | 10.18725/OPARU-1154 |
| الإتاحة: | https://doi.org/10.18725/OPARU-1154Test https://doi.org/10.1128/MCB.01966-07Test https://oparu.uni-ulm.de/xmlui/123456789/1181Test http://nbn-resolving.de/urn:nbn:de:bsz:289-vts-65481Test |
| حقوق: | Standard (Fassung vom 03.05.2003) ; https://oparu.uni-ulm.de/xmlui/license_v1Test |
| رقم الانضمام: | edsbas.B046F7B3 |
| قاعدة البيانات: | BASE |
| DOI: | 10.18725/OPARU-1154 |
|---|