MYC is a transcription factor that is often found deregulated in cancer. Post-translational modifications, including phosphorylation and ubiquitination, play important role in controlling MYC expression and activity. 

This thesis investigates the in vivo effect of the cancerous inhibitor of protein phosphatase 2A (CIP2A)-regulated phosphorylation of MYC. Here, I find that phosphorylation of MYC at serine 62 (pS62MYC) recruits MYC to Lamin A/C-associated structures. In mouse model, CIP2A-mediated phosphorylation of MYC at S62 is connected to MYC-dependent initiation of proliferation, and support of intestinal regeneration in response to DNA damage. 

The study also identified ubiquitin protein ligase E3 component nrecognin 5 (UBR5) as a novel E3 ligase for MYC. UBR5 promotes MYC degradation by ubiquitination. Functionally, UBR5 defines MYC-dependent phenotypes both in normal and in cancer cells. In drosophila, inhibition of UBR5/HYD causes MYC-overgrowth of wing imaginal discs. In cancer cells, UBR5 keeps MYC expression level below the apoptotic priming threshold. Taken together, these results give us further understanding of the role of post-translational modifications in regulating MYC activity in normal tissue growth and regeneration, as well as in cancer.