Transcriptional regulation and transformation by Myc proteins

Abstract

Myc genes comprise a small, multi-gene family and are implicated in the genesis of many different human tumours. Enhanced expression of Myc genes promotes unrestricted proliferation and contributes to many aspects of the tumour-cell phenotype. Myc proteins are transcription factors and form obligate heterodimers with Max. They activate and repress large groups of mammalian genes by recruiting histone-modifying and chromatin-remodelling enzymes. Important Myc target genes include cell-cycle regulatory genes, genes involved in protein biosynthesis and genes involved in specific metabolic pathways. Surprisingly, Myc target genes also comprise genes transcribed by RNA polymerases I and III. The stability and function of Myc proteins is regulated by Ras-dependent signalling pathways. Transformation by Myc proteins is inhibited by fail-safe mechanisms such as apoptosis. Precisely how Myc induces apoptosis remains unresolved, but Myc-induced genomic instability might play an important part in this process.