v-Myb proteins and their oncogenic potential: A study on how two point mutations affect the interaction of v-Myb with other proteins

ISBN-13: 9783656200055 / Angielski / Miękka / 2012 / 124 str.

Beeke Wienert

Opis

Master's Thesis from the year 2011 in the subject Biology - Micro- and Molecular Biology, grade: 1,0, University of Munster (Institut fur Biochemie), language: English, abstract: The oncogene v-myb of the retroviruses AMV (avian myeloblastosis virus) and E26 (avian leukaemia virus) encodes a transcription factor (v-Myb) which is a truncated homolog of its cellular progenitor c-Myb. c-Myb plays an essential role in the development of haematopoietic cells and is known to be a regulator for many target genes. v-Myb AMV is responsible for the transformation of myelomonocytic cells and arrests them in an immature stage, presumably by deregulating the expression of specific target genes. In addition to truncation of the coding region a number of amino acid (aa) substitutions are responsible for the high oncogenicity of v-Myb AMV. Due to the aa substitutions v-Myb AMV and v-Myb E26 differ in their target gene spectrum. Surprisingly, the chicken mim-1 gene can be activated by v-Myb E26 and c-Myb but not by v-Myb AMV. Recently it was shown that two aa substitutions in a hydrophobic patch in the transactivation domain of v-Myb AMV are sufficient to disrupt its ability to stimulate the Myb-responsive enhancer in mim-1. This thesis focused on the consequences of these aa substitutions at the level of protein-protein interactions particularly investigating the hydrophobic regions of v-Myb AMV and v Myb E26. In this study a cytosolic variant of GRP78, GRP78va, was confirmed to interact with both v-Myb proteins. It was shown that its interaction site is limited to a small region of v-Myb preceding the hydrophobic patch. Additionally, it was shown that GRP78va also associated with other members of the Myb-family. Furthermore, reporter gene experiments demonstrated a repressing effect of GRP78va on the transactivation potential of v-Myb E26. Two other proteins were tested for their interaction with the hydrophobic patch of v-Myb. Co-immunoprecipitation experiments confirmed that CC

O autorze

Beeke Eienert, M.Sc., was born in Bremen in 1985. After finishing a Bachelor s degree in Biology and Chemistry at the Carl-von-Ossietzky Universität Oldenburg, she completed her Master s degree in Biowissenschaften in 2011. During a research stay in Australia, the author focused on researching transcription factors. She continued to focus on these in her Master s thesis and plans to further work within this research area in her doctoral dissertation at the UNSW, Sydney.