Publikationsserver der RWTH Aachen University
Genregulation des Zellzyklusmediators Cyclin E2 in humanen und murinen Hepatomzellen
Abstract
dc:descriptionCyclins E1 and E2 are required for transition of quiescent cells into cell cycle progression. Recent data show that both E-Cyclins have a regulatory effect on each other. Especially the overexpression of Cyclin E2 in liver leads to inhibition of Cyclin E1 and reduces cell proliferation of hepatocytes. In order to understand the mechanisms and regulatory elements which control Cyclin E2-expression, the mouse Cyclin E2-promotor was analyzed. A 2 kb DNA-fragment 5-proximal of the transcription start was isolated and ligated into the Luciferase-Vector. Via sequential 5-3-depletions of this construct it was possible to localize a promotor region of 89 bp, which is essential for Cyclin E2-expression in hepatocytes. Potential binding sites for transcription factors E2F, p107, c-myb and c-myc could be identified with help of database analysis. EMSA-analysis results indicated binding of E2F3, p107 and c-myb. Additional EMSA-analysis with in vivo-samples of mice segregated before and after partial hepatectomy showed furthermore that at least five protein-complexes bind cell cycle-dependent this highly-regulated sequence. In vitro-mutagenesis of the detected E2F-binding site surprisingly caused a higher promotor activity, which indicates an inhibiting E2F-element that represses Cyclin E2. Cell cycle-dependent experiments in synchronized hepatocytes showed that this element is important for the periodic regulation of Cyclin E2. Summary: the mouse Cyclin E2-promotor was isolated and essential regulatory elements for basal and induced promotor activity were identified. These data are potentially important for diagnosis and therapy of liver diseases, because Cyclin E2-expression affects the efficiency of liver regeneration and development of cancer.
Degree
thesis:*- Grantor dc:publisher
- Publikationsserver der RWTH Aachen University
- Year dc:date
- 2010
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Hoffmann, Anke
- Contributors dc:contributor
-
- Liedtke, Christian
Subjects
dc:subject × 7Rights
dc:rights- Statement dc:rights
-
- info:eu-repo/semantics/openAccess
- Language dc:language
- ger
Identifiers
dc:identifier.*- OAI identifier oai:identifier
- oai:publications.rwth-aachen.de:63108