Myc oncogenes: the enigmatic family

Abstract

The myc family of proto-oncogenes is believed to be involved in the establishment of many types of human malignancy. The members of this family have been shown to function as transcription factors, and through a designated target sequence bring about continued cell-cycle progression, cellular immortalization and blockages to differentiation in many lineages. However, while much of the recent work focusing on the c-myc oncogene has provided some very important advances, it has also brought to light a large amount of conflicting data as to the mechanism of action of the gene product. In this regard, it has now been shown that c-myc is effective in transcriptional repression as well as transcriptional activation and, perhaps more paradoxically, that it has a role in programmed cell death (apoptosis) as well as in processes of cell-cycle progression. In addition, particular interest has surrounded the distinct roles of the two alternative translation products of the c-myc gene, c-Myc 1 and c-Myc 2. The intriguing observation that the ratio of c-Myc 1 to c-Myc 2 increases markedly upon cellular quiescence led to the discovery that the enforced expression of the two proteins individually showed that c-Myc 2 stimulates cell growth, whereas c-Myc 1 appears to be growth suppressing. Clearly, the disparities in the activities of c-Myc, together with the consistent occurrence of mutations of c-myc in human malignancies, means that, although reaching an understanding of the functions of the myc gene family might not be simple, it remains well worthy of pursuit.