Myc-nick: a cytoplasmic cleavage product of Myc that promotes alpha-tubulin acetylation and cell differentiation.

Publication Type:

Journal Article

Source:

Cell, Volume 142, Issue 3, p.480-93 (2010)

Keywords:

2010, ACETYLATION, Animals, Basic Sciences Division, Cell Differentiation, Cell Line, Tumor, Cells, Cultured, Center-Authored Paper, Comparative Medicine Core Facility, Cytosol, Genomics Core Facility, Humans, MICE, Proteomics Core Facility, Proto-Oncogene Proteins c-myc, Rats, Scientific Imaging Core Facility, Shared Resources, tubulin

Abstract:

The Myc oncoprotein family comprises transcription factors that control multiple cellular functions and are widely involved in oncogenesis. Here we report the identification of Myc-nick, a cytoplasmic form of Myc generated by calpain-dependent proteolysis at lysine 298 of full-length Myc. Myc-nick retains conserved Myc box regions but lacks nuclear localization signals and the bHLHZ domain essential for heterodimerization with Max and DNA binding. Myc-nick induces alpha-tubulin acetylation and altered cell morphology by recruiting histone acetyltransferase GCN5 to microtubules. During muscle differentiation, while the levels of full-length Myc diminish, Myc-nick and acetylated alpha-tubulin levels are increased. Ectopic expression of Myc-nick accelerates myoblast fusion, triggers the expression of myogenic markers, and permits Myc-deficient fibroblasts to transdifferentiate in response to MyoD. We propose that the cleavage of Myc by calpain abrogates the transcriptional inhibition of differentiation by full-length Myc and generates Myc-nick, a driver of cytoplasmic reorganization and differentiation.