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Functional analyses of compartmentalized binary Myc interactions / submitted by Ruth Röck
VerfasserRöck, Ruth
Betreuer / BetreuerinnenBister, Klaus ; Stefan, Eduard ; Hartl, Markus
Umfang118 S. : Ill., graph. Darst.
HochschulschriftInnsbruck, Univ., Master-Arb., 2015
Datum der AbgabeFebruar 2015
Schlagwörter (GND)Myc / Genexpression / Zellkultur / Inhibitorproteine / Proliferation
URNurn:nbn:at:at-ubi:1-1946 Persistent Identifier (URN)
 Das Werk ist frei verfügbar
Functional analyses of compartmentalized binary Myc interactions [4.39 mb]
Zusammenfassung (Englisch)

c-Myc is a member of the bHLH-LZ protein family which needs to heterodimerize with Max to perform its critical functions as a transcription factor. Thereby it regulates growth, cell proliferation, DNA replication, cell cycle progression, differentiation, and metabolism. Deregulation of Myc expression contributes to the etiology and progression of cancer. Due to its huge impact on cellular processes, deregulated Myc signaling occurs in almost all types of human cancer. In addition to c-Myc, the variants v-Myc, N-Myc, L-Myc have been studied intensively. In this work, differences of the oncogenic potentials of the Myc variants were analyzed using transformation assays based on avian cell culture systems. v-Myc displayed the highest transforming potential followed by N-Myc, c-Myc, and L-Myc. The transformation potential correlates with the protein-protein interaction (PPI) pattern which was quantified using a protein fragment complementation assay (PCA). In addition to the studies of Myc:Max Renilla Luciferase (RLuc) PCA dynamics using cellular second messenger molecules, the subcellular localization using Venus YFP (Ven) PCA was determined. Besides nuclear localization of Myc332-439:Max and Max:Max, we showed for the first time that Ven PCA tagged full length Myc:Max complexes are restricted to the nucleus of quail embryonic fibroblasts. Finally, a new PPI was analyzed which might link BASP1 functions to Myc signaling. The Myc target gene BASP1 is known to inhibit Myc-induced cell transformation. Calmodulin (CaM) interacts with BASP1 and could be functionally connected to BASP1-mediated Myc inhibition. We have characterized the binding interface of the Myc:CaM PPI, which involves the basic region of Myc. We believe that targeting known and new PPIs of Myc is a promising strategy to reduce Myc variant driven cell proliferation.

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