Cancerous cells often exhibit not only a capacity for excessive proliferation but also a resistance to apoptosis. For example, the oncoprotein c-MYC, an important contributor to many human tumors, activates the transcription of some genes and represses that of others and thus influences many target genes that might contribute to the regulation of apoptosis. Patel and McMahon have extended earlier studies that showed that the binding of c-Myc to the transcription factor MIZ-1 and the inhibition of MIZ-1-dependent transcription were important for promoting apoptosis. In human fibroblasts, a form of c-MYC (c-MYCV394D) that does not interact with MIZ-1 was defective in inducing apoptosis. Furthermore, when the level of MIZ-1 was reduced in these cells, the apoptotic effect of c-MYCV394D was restored. MIZ-1 activates the transcription of several hundred genes, and a search of target genes in microarrays yielded a promising candidate: the gene encoding the antiapoptotic protein BCL2. Indeed, expression of BCL2 was decreased by c-MYC but not by c-MYCV394D, and inhibiting BCL2 expression rescued the ability of c-MYCV394D to promote apoptosis. Previous studies of mouse models and of human tumor cells have shown that BCL2 and c-MYC appear to work together in promoting cancer, and these results indicate that transcription of the BCL2 gene is regulated through c-MYC and MIZ-1. — LBR
J. Biol. Chem. 282, 5 (2007).