Review Redefines the Role of MYC in Carcinogenesis

A recent review article that summarized research on the transcription factor MYC revealed that while the MYC protein binds to about 15% of all genes, it does not always activate the genes to which it binds.

N-MYC is a member of the MYC gene family, which contains at least seven closely related genes (C-MYC, N-MYC, L-MYC, P-MYC, R-MYC, S-MYC and B-MYC). The principle functions of MYC are the induction of proliferation and the inhibition of terminal differentiation in certain cells. The human N-MYC gene spans 6-7 kb of genomic DNA and is located on chromosome 2p24.1. The N-MYC proteins have a molecular weight of 65 and 67 kDa.

The gene that codes for synthesis of the MYC protein is the most overexpressed oncogene found in human cancers. Investigators at the Wistar Institute (Philadelphia, PA, USA; www.wistar.upenn.edu) recently reviewed the status of research on MYC for the July 2004 issue of Nature Reviews Cancer. They found that while MYC binds to as many as 15% of all genes, binding alone does not always activate the gene. This observation calls into question long-held assumptions about MYC's functioning and opens new directions for MYC research.

"Previous studies looked at which genes are bound by MYC, and it turns out to be a great percentage of genes--one out of every six,” said senior author Dr. Steven McMahon, an assistant professor at the Wistar Institute. "Our work has extended what these studies hinted at: contrary to what was believed, MYC does not always turn on the genes to which it binds. The implication is that just figuring out which genes bind to MYC will not be enough to tell us what pathways are being activated in cancer. There must be other factors that play a role in whether MYC activates a gene.”



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