Dept. of Molecular and Medical Genetics
Oregon Health & Science University
c-Myc is a pleiotropic transcription factor that regulates hematopoiesis, and high levels of c-Myc are frequently found in human leukemia. c-Myc protein levels are controlled in part by the phosphorylation of two N-terminal residues, serine 62 (S62) and threonine 58 (T58), and phosphorylation of these residues controls c-Myc protein stability. Based on these findings, I hypothesized that increased c-Myc protein stability is partly responsible for high c-Myc levels in leukemia. In this dissertation, I describe the discovery of increased c-Myc protein stability in both lymphoid and myeloid leukemia coupled to altered phosphorylation of c-Myc at S62 and T58. In addition, I have found that this altered protein stability and phosphorylation can occur through multiple mechanisms, including the constitutive activation of upstream signaling pathways and the deregulation of proteins that promote c-Myc degradation. Lastly, I investigated the effects of overexpressing one of these proteins, AXIN
School of Medicine
Tibbitts, Deanne Carol, "Characterization of aberrant c-Myc phosphorylation and stability in acute myeloid and lymphoblastic leukemia" (2011). Scholar Archive. 672.