An evolutionarily acquired genotoxic response discriminates MyoD from Myf5, and differentially regulates hypaxial and epaxial myogenesis

被引：14

作者：

Innocenzi, Anna ^{[3
]}

Latella, Lucia ^{[1
,2
]}

Messina, Graziella ^{[3
,4
]}

Simonatto, Marta ^{[1
,2
]}

Marullo, Fabrizia ^{[1
,2
]}

Berghella, Libera ^{[5
]}

Poizat, Coralie ^{[6
,7
,8
]}

Shu, Chih-Wen ^{[9
,10
]}

Wang, Jean Y. J. ^{[10
]}

Puri, Pier Lorenzo ^{[1
,2
,9
]}

Cossu, Giulio ^{[3
,4
]}

机构：

[1] IRCCS Fdn Santa Lucia, Dept Epigenet & Regenerat Med, Dulbecco Telethon Inst, I-00143 Rome, Italy

[2] European Brain Res Inst, I-00143 Rome, Italy

[3] Ist Sci San Raffaele, Div Regenerat Med, I-20132 Milan, Italy

[4] Univ Milan, Dept Biol, I-20133 Milan, Italy

[5] Casa di Cura San Raffaele Sulmona, Laquila, Italy

[6] King Faisal Specialist Hosp & Res Ctr, Riyadh 11211, Saudi Arabia

[7] Univ So Calif, Keck Sch Med, Inst Med Genet, Los Angeles, CA 90033 USA

[8] Univ So Calif, Keck Sch Med, Dept Biochem & Mol Biol, Los Angeles, CA 90033 USA

[9] Sanford Burnham Inst Med Res, La Jolla, CA 92037 USA

[10] Moores UCSD Canc Ctr, Dept Med, Div Hematol Oncol, La Jolla, CA 92093 USA

来源：

EMBO REPORTS | 2011年 / 12卷 / 02期

基金：

欧洲研究理事会;

关键词：

DNA damage; skeletal myogenesis; Myo D; Myf5; cAbl kinase; DNA-DAMAGE; ACTIVATION; CELLS;

D O I：

10.1038/embor.2010.195

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Despite having distinct expression patterns and phenotypes in mutant mice, the myogenic regulatory factors Myf5 and MyoD have been considered to be functionally equivalent. Here, we report that these factors have a different response to DNA damage, due to the presence in MyoD and absence in Myf5 of a consensus site for Abl-mediated tyrosine phosphorylation that inhibits MyoD activity in response to DNA damage. Genotoxins failed to repress skeletal myogenesis in MyoD-null embryos; reintroduction of wild-type MyoD, but not mutant Abl phosphorylation-resistant MyoD, restored the DNA-damage-dependent inhibition of muscle differentiation. Conversely, introduction of the Abl-responsive phosphorylation motif converts Myf5 into a DNA-damage-sensitive transcription factor. Gene-dosage-dependent reduction of Abl kinase activity in MyoD-expressing cells attenuated the DNA-damage-dependent inhibition of myogenesis. The presence of a DNA-damage-responsive phosphorylation motif in vertebrate, but not in invertebrate MyoD suggests an evolved response to environmental stress, originated from basic helix-loop-helix gene duplication in vertebrate myogenesis.

引用

页码：164 / 171

页数：8