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 journalArticle

136 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 1 2010

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Keywords

  • CELLBIO
  • PROTEINS

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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