Writing and erasing MYC ubiquitination and SUMOylation

Abstract The transcription factor c-MYC (MYC thereafter) controls diverse transcription programs and plays a key role in the development of many human cancers. Cells develop multiple mechanisms to ensure that MYC levels and activity are precisely controlled in normal physiological context. As a short half-lived protein, MYC protein levels are tightly regulated by the ubiquitinproteasome system. Over a dozen of ubiquitin ligaseshave been found to ubiquitinateMYC whereas a number of deubiquitinating enzymescounteract this process. Recent studies show that SUMOylation and deSUMOylation can also regulate MYC protein stability and activity. Interestingly, evidence suggests an intriguing crosstalkbetween MYC ubiquitinationand SUMOylation. Deregulation of the MYC ubiquitination-SUMOylation regulatory network may contribute to tumorigenesis. This review is intended to provide the current understanding of the complex regulation of the MYC biology by dynamic ubiquitinationand SUMOylation and their crosstalk.