Myc on my mind: a transcription factor family's essential role in brain development

www.impactjournals.com/oncotarget 86 Oncotarget 2010; 1: 86-88 Researchers have been captivated by the myc family of proto-oncogenes and their ability to regulate a diverse array of cellular processes through transcriptional regulation of target genes. Since the early 1980s researchers have worked to understand how Myc family members regulate hundreds of genes in a contextdependent and cell type-specific manner. Gene expression profiling performed in various overexpression platforms have identified hundreds of genes regulated by Myc but have done little to narrow the focus of Myc’s function as the genes typically fall into multiple biological categories, including protein biosynthesis, metabolism, cell cycle regulation and microRNAs [1, 2]. In order to parse the cell type-specific function of Myc proteins, future studies will benefit from the generation of mouse models wherein gene manipulation can be restricted to specific cell types. Mammals possess three closely related myc family members: c-, N-, and L-myc, which have developmentally regulated, tissue specific expression patterns. These proteins, basic-helix-loop-helix zipper (bHLHZ) transcription factors, heterodimerize with the ubiquitously-expressed Max protein to activate gene expression. In complex with another protein, Miz1, myc may suppress gene expression [3, 4]. Myc has been predicted with gene promoters, including those that control cell cycle regulation, apoptosis, differentiation programs as well as chromatin remodeling [1, 5]. More recently Myc proteins have also been shown to regulate genes involved in ribosome biosynthesis and other components involved in protein translation [6], suggesting that Myc’s roles in cellular processes extend beyond cell cycle and apoptosis regulation. Furthermore, Myc’s ability to cooperate with three other transcription factors (Oct4, Sox2 and Klf4) to reprogram somatic cells to induced pluripotent stem cells suggests Myc proteins have critical roles in maintaining cells in an undifferentiated state [7, 8]. The role for Myc proteins in proliferation has been well documented in mammals through embryonic and Myc on my mind: a transcription factor family’s essential role in brain development