Effects of Myc inhibition/knockout on normal tissues and cells

The three Myc proteins, c-Myc, L-Myc and N-Myc, are all basic helix-loop-helix (bHLH)-Zip transcription factors that coordinate cell proliferation, cell cycle progression, cell growth, metabolism, differentiation and tissue remodel ing, as well as a variety of protective checkpoint mechanisms such as growth arrest and apoptosis. Myc proteins form heterodimers with their bHLH-Zip partner Max, transactivating genes by binding at canonical E-Box CAC/ATG recognition elements in target gene promoters and repressing other genes through interactions with the zinc finger protein Miz-1 and/or recruitment of the DNA methyltransferase corepressor Dnmt3a (Figure 1) [1]. Expression array, SAGE, chromatin IP, promoter scanning and whole cell proteomic approaches identify thousands of Myc target genes with diverse roles in virtually every aspect of cell and tissue behavior, including growth, metabolism, cell cycle, differentiation, telomere maintenance, DNA damage and repair, intracellular membrane transport, cytoskeleton, cyto kine production, angiogenesis, invasion and apoptosis [2] (see also http://www.myc-cancer-gene.org/ site/mycTargetDB.asp).