Abstract A08: Identification of c-MYC SUMOylation by mass spectrometry

The c-MYC transcription factor is a master regulator of many cellular processes and deregulation of this oncogene has been linked to more than 50% of all cancers. In normal cells, MYC is tightly controlled at a number of steps, including at the transcriptional, translational and post-translational levels. Altered regulation at any of these steps can result in deregulated, oncogenic MYC. One well-studied canonical pathway that is known to regulate MYC activity and stability at the post-translational level is the GSK3 pathway. The GSK3-FBXW7 axis regulates MYC via phosphorylation at T58, followed by ubiquitylation of MYC by the E3 ubiquitin ligase complex SCF-FBXW7 and subsequent proteasomal degradation. Accordingly, substituting threonine 58 with alanine (T58A) confers increased stability and transformative potential. Thus, characterizing the post-translational modifications (PTMs) of MYC can lead to a better understanding of the regulatory mechanisms controlling this potent oncogene. SUMOylation is a post-translational modification that utilizes a series of E1, E2 and E3 proteins for conjugation of a small ubiquitin-like modifier (SUMO) moiety to its target protein. Growing evidence indicates that SUMOylation has many important roles in the cell, such as response to cellular stressors and transcriptional regulation. Moreover, recent reports have unveiled a potential role for SUMOylation in MYC-driven tumourigenesis. Here, using immunoprecipitation combined with mass spectrome...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Myc Function and Phosphorylation - Ubiquitination: Poster Presentations - Proffered Abstracts Source Type: research