Myc-Nick: A Cytoplasmic Cleavage Product of Myc that Promotes α-Tubulin Acetylation and Cell Differentiation

SummaryThe 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 α-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 α-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.

Graphical AbstractFigure optionsDownload high-quality image (111 K)Download as PowerPoint slideHighlights
► Calpain cleavage truncates N- and c-Myc oncoproteins to produce Myc-nick
► Myc-nick is cytoplasmic and lacks nuclear localization and DNA-binding domains
► Myc-nick complexes with tubulins and the HAT GCN5 to promote α-tubulin acetylation
► Myc-nick promotes changes in cell morphology and accelerates muscle differentiation