Mechanisms of MYC stabilization in human malignancies

Abstract

MYC is a pleiotropic transcription factor that has been linked to a diverse range of cellular functions, such as cell cycle regulation, proliferation, growth, differentiation and metabolism. Not surprisingly, aberrant MYC signaling has been observed in human cancers and MYC has been demonstrated to promote cell transformation and tumor progression. Here we discuss recent discoveries that have expanded our knowledge of MYC protein stability. In particular we focus on mechanisms that might explain the increased stability of MYC often observed in human cancers and cell lines. We also summarize our recent characterization of Cancerous inhibitor of PP2A (CIP2A/KIAA1524) as a protein that inhibits PP2A-mediated MYC dephosphorylation and proteolytic degradation. Finally, we discuss the potential relevance of mechanisms that regulate MYC stability for tumor formation in the context of cancer therapy. ©2008 Landes Bioscience.