期刊
EMBO REPORTS
卷 12, 期 2, 页码 164-171出版社
WILEY
DOI: 10.1038/embor.2010.195
关键词
DNA damage; skeletal myogenesis; Myo D; Myf5; cAbl kinase
资金
- Associazione Italiana Ricerca sul Cancro (AIRC)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [RO1AR052779]
- European Community
- European Research Council (ERC)
- Fondo Istituzionale Ricerca di Base (FIRB)
- Telethon
- Duchenne Parent Project
- Italian Ministries of Research and Health
- Compagnia San Paolo di Torino
- Wright Foundation
- American Heart Association
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据