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

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

doi:10.1016/j.cell.2010.06.037

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 journal › Article › peer-review

172 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 language	English (US)
Pages (from-to)	480-493
Number of pages	14
Journal	Cell
Volume	142
Issue number	3
DOIs	https://doi.org/10.1016/j.cell.2010.06.037
State	Published - Aug 2010

Keywords

CELLBIO
PROTEINS

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/j.cell.2010.06.037

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

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.",

keywords = "CELLBIO, PROTEINS",

author = "Maralice Conacci-Sorrell and Celine Ngouenet and Eisenman, {Robert N.}",

note = "Funding Information: We are grateful to Nao Ikegaki, William Tansey, John Sedivy, and Peter Hurlin for reagents essential for this work. We also thank Stephen Tapscott, Maura Parker, Hector Rincon, Bill Carter, Linda Wordeman, and members of the Eisenman lab for advice and discussion. M.C.-S. was a recipient of an EMBO Long-Term Fellowship. This work was supported by NIH/NCI grant CA20525 (R.N.E.). ",

year = "2010",

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AU - Ngouenet, Celine

AU - Eisenman, Robert N.

N1 - Funding Information: We are grateful to Nao Ikegaki, William Tansey, John Sedivy, and Peter Hurlin for reagents essential for this work. We also thank Stephen Tapscott, Maura Parker, Hector Rincon, Bill Carter, Linda Wordeman, and members of the Eisenman lab for advice and discussion. M.C.-S. was a recipient of an EMBO Long-Term Fellowship. This work was supported by NIH/NCI grant CA20525 (R.N.E.).

PY - 2010/8

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N2 - 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.

AB - 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.

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

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