E2A protein degradation by the ubiquitin-proteasome system is stage-dependent during muscle differentiation

被引:18
作者
Sun, L.
Trausch-Azar, J. S.
Ciechanover, A.
Schwartz, A. L.
机构
[1] Washington Univ, Sch Med, Edward Mallinckrodt Dept Pediat, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Dept Mol Biol & Pharmacol, St Louis, MO 63110 USA
[3] St Louis Childrens Hosp, St Louis, MO 63178 USA
[4] Technion Israel Inst Technol, Fac Med, Vasc & Tumor Biol Res Ctr, Haifa, Israel
基金
美国国家卫生研究院;
关键词
E2A; E12; E47; ubiquitin; proteasome; muscle differentiation;
D O I
10.1038/sj.onc.1209793
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
The E2A proteins are basic helix-loop-helix transcription factors that regulate proliferation and differentiation in many cell types. In muscle cells, the E2A proteins form heterodimers with muscle regulatory factors such as MyoD, which then bind to DNA and regulate the transcription of target genes essential for muscle differentiation. We now demonstrate that E2A proteins are primarily localized in the nucleus in both C2C12 myoblasts and myotubes, and are degraded by the ubiquitin proteasome system evidenced by stabilization following treatment with the proteasome inhibitor, MG132. During the differentiation from myoblast to myotube, the cellular abundance of E2A proteins is relatively unaltered, despite significant changes ( each similar to 5-fold) in the relative rates of protein synthesis and protein degradation via the ubiquitin-proteasome system. The rate of ubiquitin-proteasome-mediated E2A protein degradation depends on the myogenic differentiation state (t 1/2 similar to 2 h in proliferating myoblasts versus t 1/2 > 10h in differentiated myotubes), and is also associated with cell cycle in non-muscle cells. Our findings reveal an important role for both translational and post-translational regulatory mechanisms in mediating the complex program of muscle differentiation determined by the E2A proteins.
引用
收藏
页码:441 / 448
页数:8
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