Microarray analysis of MYC-mediated death response pathways

The proto-oncogene MYC plays an important role in the control of proliferation, differentiation and apoptosis and its aberrant expression is commonly found in human cancers. Very little is known about genes involved in MYC pro-apoptotic functions. A recent study set out to identify the role of MYC in DNA-damage-mediated apoptosis, by comparing gene expression profiles of wild-type and MYC-null cells after DNA damage by VP16.Yu et al. [1xSee all References[1] identified two gene clusters that were associated with VP16-induced apoptosis. Of these two, only one, which includes c-JUN, was highly regulated by MYC and appeared to be crucial for the maximal apoptotic response in wild-type cells. The authors show that MYC levels dropped sharply following VP16 exposure, resulting in induction of genes of the MYC-responsive cluster. They conclude that removal of MYC-mediated repression of apoptotic signals is part of the mechanism by which MYC mediates a complete and rapid cell death following DNA damage.The implication of this conclusion is that any cell that has low MYC levels would therefore be more prone to undergo apoptosis. This seems to be in contrast with the biological notion that MYC sensitizes cells to undergo apoptosis simultaneously with cell proliferation, thus ensuing that only cells without any defect and in the right environment are allowed to divide, whereas cells that encountered DNA damage or lack trophic support as a result of being in the wrong environment, will die by apoptosis. It will therefore be very interesting to see if the genes identified as cluster C in this study play a role in MYC sensitization to different pro-apoptotic triggers, such as serum deprivation and death receptor signaling.