Study of molecular mechanisms causing v-Myb suppression using proteomics-based approach

Information

This project doesn't include Faculty of Medicine. It includes Faculty of Science. Official project website can be found on muni.cz.

Investor logo
Project Identification
GA301/03/1055
Project Period
1/2003 - 1/2005
Investor / Pogramme / Project type
Czech Science Foundation
MU Faculty or unit
Faculty of Science
Keywords
Myb, proteomics, differentiation, tumor suppression

The v-myb oncogene of avian myeloblastosis virus causes acute myeloblastic leukemia in vivo and transforms myelomonocytic cells in vitro. It codes for a v-Myb transcription factor that changes expression pattern of its target genes and/or interacts with other proteins, thus causing transformation of the cell. The model line of v-Myb-transformed monoblasts BM2 can undergo terminal differentiation, growth arrest and/or apoptosis in response to extracellular stimuli, such as phorbol esters, trichostatin A and retinoic acid. Sensitivity of BM2 cells to these agents can be significantly affected by ectopic expression of certain genes (RAR, RXR, c-myb, v-jun, c-jun, v-fos, c-fos, CBP, p300, p53, bcl-2). These effects result from specific interaction of the v-Myb protein and/or its target gene products with cellular signaling pathways directed by these inducers. The aim of this project is to investigate the network of intracellular pathways that possess decisive role in leukemogenesis induced by v-Myb oncoprotein. It takes advantage of avilability of the set of BM2 derivatives expressing single transgenes created in our laboratory and proposes to use them in exploring molecular mechansims responsible for v-myb suppression in BM2 cells by proteomics approach. Comparison of two-dimensional electrophoretograms of proteins purified from BM2 cells induced to differentiate and from untreated controls would suggested the differentially expressed proteins to be identified by mass spectrometry. Understanding of cellular molecular pathways causing suppression of the oncoprotein has important implication for selection of targets for anti-cancer therapies.

Publications

Total number of publications: 23


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