Myc's broad reach

Abstract

The role of the myc gene family in the biology of normal and cancer cells has been intensively studied since the early 1980s. myc genes, responding to diverse external and internal signals, express transcription factors (c-, N-, and L-Myc) that heterodimerize with Max, bind DNA, and modulate expression of a specific set of target genes. Over the last few years, expression profiling, genomic binding studies, and genetic analyses in mammals and Drosophila have led to an expanded view of Myc function. This review is focused on two major aspects of Myc: the nature of the genes and pathways that are targeted by Myc, and the role of Myc in stem cell and cancer biology.

Figure 1.

Summary of the functional categories of genes whose expression is modulated by augmented Myc expression. This information is derived primarily from gene expression profiling studies employing microarrays (see the text for details and references).

Figure 2.

Transcriptional complexes associated with Myc. Depicted are individual coregulator complexes known to interact with Myc. In principle, several complexes could simultaneously associate with single Myc proteins. The binding of a Myc-Max heterodimer to the Miz-1 is shown, resulting in repression through inhibition of nucleophosmin (NPM). Many other protein interactions have been described for Myc (see the text).

Figure 3.

Myc influences self-renewal and differentiation of stem cells. The effects of Myc on expression of genes considered critical for differentiation and proliferation are indicated. See the text for details.