Myc-nick: A cytoplasmic cleavage product of Myc that promotes α-tubulin acetylation and cell differentiation

Maralice Conacci-Sorrell, Celine Ngouenet, Robert N. Eisenman

Research output: Contribution to journalArticlepeer-review

147 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)480-493
Number of pages14
JournalCell
Volume142
Issue number3
DOIs
StatePublished - Aug 2010

Keywords

  • CELLBIO
  • PROTEINS

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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