The transcriptional activator and oncoprotein c-MYC plays a prominent role in cancer and has been implicated in the regulation of fundamental cellular events such as cell cycle control, proliferation, differentiation and apoptosis.
More recently MYC has been shown to play a pivotal role in the regulation of protein synthesis and cell mass (cell growth). Indeed, characterization of c-MYC transcriptional targets indicates that the majority of genes regulated by this factor are associated with various aspects of ribosome assembly and function.
We were the first to demonstrate that c-MYC can regulate the key component and major rate-limiting step in ribosome biogenesis, the transcription of the 45S rRNA gene and the 5S gene whose products together constitute the rRNA. These observations provide a mechanism to link MYC to ribosome biogenesis, the major determinant of proliferation rates in mammalian cells.
An increasing body of research supports a role for the deregulation of ribosome biogenesis in malignant transformation leading to the intriguing hypothesis that many of the phenotypic effects of MYC including its oncogenic potential are related to its ability to modulate ribosome biogenesis and ribosome function.
This proposal will directly test this hypothesis using a transgenic model of B-cell lymphoma. The outcomes of such investigations have the potential to provide new insights into the coordination of growth with proliferation and provide potentially novel therapeutic treatments for cancer related disease.