A functional hierarchy for c-Myc target genes? Lessons from MT-MC1

Deregulation of CMYC is a hallmark of many human cancers. As a general bHLH-ZIP transcription factor, the c-Myc oncoprotein directly regulates the expression of >1500 genes controlled by RNA polymerases I, II and III. This represents a formidable challenge to determining which are the most critical for transformation. Previous work from our laboratory has indicated that MT-MC1, a direct c-Myc target gene, mimics many c-Myc phenotypes. More recently, genome-wide microarray experiments indicate that MT-MC1 itself regulates fewer than 50 downstream target genes, many of which, if not all, are also c-Myc targets. These observations suggest that this small, overlapping subset of target genes plays a particularly important role in c-Myc-mediated transformation. This is supported by the finding that nearly half of MT-MC1-regulated genes have been previously implicated in cancer.