Cytokine-induced Inhibition of Myc Activity in Monocytic Cells
The c-myc proto-oncogene plays an important role in the regulation of cell proliferation, differentiation and apoptosis. It encodes a transcription factor of the basic region/helix-loop-helix/leucine zipper (bHLHZip) family and binds specifically to certain E-box DNA elements and activates transcription from promoters containing such elements by forming heterodimers with the bHLHZip protein Max (Blackwood et al. 1991, Prendergast et al. 1991, for review see Henriksson and Lüscher 1996). Max on the other hand was recently shown to form heterodimers with a number of other bHLHZip proteins; Mad1, Mxi1, Mad3 and Mad4, referred to as the Mad family (Ayer et al. 1993, Zervos et al. 1993, Hurlin et al. 1995a). These are, like c-Myc, dependent on Max for their activity and bind the same DNA elements as Myc:Max heterodimers. The Mad proteins seem to act as negative regulators of growth and inhibit the transactivating and transforming capacity of Myc (for review see Henriksson & Lüscher 1996). This repressive activity depends on the N-terminus of Mad which is required for interaction with mammalian homologues of the yeast repressor protein Sin3 (Ayer et al. 1995, Schreiber-Agus et al. 1995).
KeywordsNonreceptor Protein Tyrosine Kinase CACGTG Sequence Mad1 mRNA Mad1 Protein Expression Monocytic Differentiation Marker
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