Charakterisierung der Interaktion zwischen der Src-Kinase Fyn und hnRNP K im Neuroblastom
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Philipps-Universität Marburg
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Abstract
The neuroblastoma is a malignant tumor, which occurs in childhood and which is mainly localized in the postganglion sympatic neuronal system. The increased expression of the Src-kinase Fyn leads in neuroblastoma cells to an induction of neuronal differentiation and to an arrest in the G1-stage of the cell cycle. The heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a protein, which interacts in-vitro as well as in in-vivo specifically with the c-Src-kinase. HnRNP K leads to a translational silencing. C-Src has a disinhibiting effect. Futhermore it was described that Fyn and hnRNP K are binding in-vitro to each other. The following was hypothesized: With the binding of hnRNP K to a specific mRNA the translation of specific proteins in neuroblastoma cells is inhibited. Fyn is able to inhibit this binding reversibly by phosphorylation of hnRNP K. Thus it launched a process of translation of proteins, which are responsible for growth-arrest and differentiation. In this thesis the attempt has been made to identify an in-vivo binding of Fyn and hnRNP K. Furthermore, it has been examined whether a phosphorylation of hnRNP K by Fyn takes place and if a possibly existing interaction has a regulating influence on the translation. In addition, the biological effects of a potential interaction were analysed. Here it was studied, if the growth-arrest und differentiation-inducing effect of Fyn is mediated by hnRNP K. In summary the obtained data demonstrate that the described interaction of c-Src-kinase and hnRNP K is non-transferable to the situation of Fyn/ hnRNP K in human neuroblastoma cells. An in-vivo binding of the two proteins could not been shown, nor was an interaction by phosphorylation verified. In the functional experiment a dereprimating influence of Fyn on the hnRNP K-mediated inhibition of the translation appeared. The presence of hnRNP K does not show an influence on Fyn-dependent neuronal differentiation and G1-arrest of the cell cycle.
In conclusion, the results do not point out that Fyn and hnRNP K can influence the pro-liferation of neuroblastoma cells by a direct interaction.
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Created: 2008Issued: 2009-01-20Updated: 2011-08-10
Faculty
Medizin
Publisher
Philipps-Universität Marburg
Language
ger
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DoctoralThesis
Keywords
hnRNP Kc-Src-kinaseNeuroblastoma cell
DFG-subjects
C-terminal-Src-KinaseNeuroblastomHeterogene Ribonucleoproteine
DDC-Numbers
610
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Deppe, Daniela Jenny: Charakterisierung der Interaktion zwischen der Src-Kinase Fyn und hnRNP K im Neuroblastom. : Philipps-Universität Marburg 2009-01-20. DOI: https://doi.org/10.17192/z2009.0013.
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This item has been published with the following license: In Copyright