How is the stability of the Myc protein, a key regulator of cell growth, precisely controlled? This research delves into the mechanisms governing Myc protein stability, demonstrating the critical role of multiple Ras-dependent phosphorylation pathways. The study focuses on two N-terminal phosphorylation sites in Myc, Thr 58 and Ser 62, known to be regulated by mitogen stimulation. The findings reveal that phosphorylation of Ser 62, likely mediated by ERK, is crucial for Ras-induced Myc stabilization. Conversely, phosphorylation of Thr 58, likely mediated by GSK-3 (dependent on prior Ser 62 phosphorylation), promotes Myc degradation. Further analysis indicates that the Ras-dependent PI-3K pathway is also vital for controlling Myc protein accumulation, likely through the regulation of GSK-3 activity. These observations define a synergistic role for multiple Ras-mediated phosphorylation pathways in controlling Myc protein accumulation during the initial stages of cell proliferation, adding to our understanding of cell growth regulation and potential therapeutic targets for cancer.
Published in _Genes & Development_, this study aligns with the journal's focus on molecular biology and developmental processes. By elucidating the regulatory mechanisms controlling Myc protein stability, the paper contributes to the understanding of fundamental cellular processes related to gene expression and cell growth, a core area of interest for the journal.