A10
Structural mechanisms underlying MYC ubiquitylation
Project Summary
In normal cells, the ubiquitin system controls the levels of proteins to enable signaling and to maintain overall homeostasis. Indeed, due to MYC regulation of cell proliferation, cell growth, stem cell self-renewal, differentiation, and apoptosis, MYC protein levels are normally tightly controlled by ubiquitylation. This balance is altered in tumor cells. Thus, it is important to understand the structural mechanisms by which E3 ligases and deubiquitylating enzymes (DUBs) collaboratively specify levels of oncoproteins such as MYC. It is also important to understand the defects in these mechanisms that drive cancers, and to discover new ways to overcome such defects. We propose to address these challenges for distinct E3 ligases and DUBs that coordinately regulate MYC.
