Identifizierung von bona fide Interaktionspartnern der Transkriptionsfaktoren c-Myc und Miz-1

Das Proto-Onkogen c-myc ist durch seine Funktion als Transkriptionsfaktor entscheidend an vielen Prozessen beteiligt, welche die zelluläre Homöostase aufrechterhalten. Wegen seiner Rolle als Aktivator und Repressor vieler Gene, führt die Deregulation der Expression von c-Myc auch zur Deregulation ph...

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Bibliographic Details
Main Author: Reese, Jens - Peter
Contributors: Renakwitz-Pohl, Renate (Prof. Dr.) (Thesis advisor)
Format: Dissertation
Published: Philipps-Universität Marburg 2008
Molekularbiologie und Tumorforschung
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Table of Contents: The proto-oncogene c-Myc is a transcription factor and is essential for the maintenance of the cellular homeostasis. Since c-Myc acts as both activator and inhibitor of transcription of many genes, it’s deregulation leads to a dysfunction in cell cycle control, cell growth or apoptosis and promotes tumor development. Like the majority of proteins Myc functions through interaction with other proteins in multi protein complexes. An important interactor of c-Myc is Miz-1, which is able to activate genes by DNA binding. c-Myc inhibits this activation through interaction with Miz-1 via an unknown mechanism. In the present study , two approaches were used to identify interaction partners of c-Myc and Miz-1: A tandem affinity purification (TAP) and a fractioning approach by chromatography. Both approaches resulted in bona fide interaction partners, which were identified by mass spectrometry. The TAP yielded Hsp 70, a heat shock protein, as potential interaction partner of Miz-1. Additionally, three different Miz-1 variants could be identified. The fractioning provided a list of 171 different bona fide binding partners of c-Myc and/or Miz-1. The identified proteins belong to factors from transcription, RNA processing, DNA repair, protein modification and degradation as well as to cell structure, metabolism and protein synthesis. The results of this study may serve as a basis for further investigation of the c-Myc/Miz-1 function not only in the well known context of transcriptional regulation, but also in other processes, which are possibly regulated by c-Myc or Miz-1 and could contribute to tumorigenesis.