SUMOylation of Pax7 is essential for neural crest and muscle development.
SUMOylation of Pax7 is essential for neural crest and muscle development.
复制标题
DOI：
10.1007/s00018-012-1220-1
复制
发表时间：
2013-05
影响因子：
8
通讯作者：
Garcia-Castro, Martin I.
中科院分区：
文献类型：
--
作者：
Luan, Zhidong;Liu, Ying;Stuhlmiller, Timothy J.;Marquez, Jonathan;Garcia-Castro, Martin I.
Pax家族的调节性转录因子在脊椎动物发育、出生后再生和癌症过程中的多能细胞功能中发挥重要作用。Pax 7及其同源物Pax 3在神经嵴和肌肉发育中起重要作用。这两种基因在各种组织中共表达，并被认为提供相似但不相同的功能。允许Pax 7特异性调节的机制在很大程度上仍然未知。在这里，我们报告的第一次，Pax 7是由SUMO化调节。我们确定了Pax 7与Ubc 9（SUMO结合酶）的相互作用，并揭示了SUMO化机制在神经嵴前体中富集，并在NC发育中起着关键作用。我们证明了Pax 7成为SUMO化，并确定了赖氨酸85（K85）在Pax 7-SUMO化中的重要作用。尽管在Pax基因中K85周围具有高度保守性，但我们无法鉴定所测试的其他Pax蛋白（包括Pax 3）的SUMO化。使用非SUMO化的Pax 7 K85 x R变体（Pax 7 K85 R），我们证明SUMO化对于Pax 7在神经嵴发育、C2 C12肌源性分化和转录反式激活中的功能是必不可少的。我们的研究为神经嵴和肌肉发育中SUMO化对Pax 7功能的分子调控提供了新的机制见解。
Regulatory transcription factors of the Pax family play fundamental roles in the function of multipotent cells during vertebrate development, post-natal regeneration, and cancer. Pax7 and its homologue Pax3 are important players in neural crest and muscle development. Both genes are coexpressed in various tissues and are thought to provide similar, but not identical functions. The mechanisms that allow specific regulation of Pax7 remain largely unknown. Here we report for the first time that Pax7 is regulated by SUMOylation. We identify the interaction of Pax7 with Ubc9, the SUMO conjugating enzyme, and reveal that SUMOylation machinery is enriched in neural crest precursors and plays a critical role in NC development. We demonstrate that Pax7 becomes SUMOylated and identify an essential role for lysine 85 (K85) in Pax7-SUMOylation. Despite high conservation surrounding K85 amongst Pax genes, we were unable to identify SUMOylation of other Pax proteins tested, including Pax3. Using a non-SUMOylatable Pax7 K85 x R variant (Pax7K85R), we demonstrate that SUMOylation is essential for the function of Pax7 in neural crest development, C2C12 myogenic differentiation, and transcriptional transactivation. Our study provides new mechanistic insight into the molecular regulation of Pax7’s function by SUMOylation in neural crest and muscle development.
登录
查看更多内容
DOI：
10.1083/jcb.200508001
发表时间：
2006-01-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kuang S;Chargé SB;Seale P;Huh M;Rudnicki MA
通讯作者：
Rudnicki MA
影响因子：
2.7
作者：
Maczkowiak, Frederique;Mateos, Stephanie;Monsoro-Burq, Anne H.
通讯作者：
Monsoro-Burq, Anne H.
影响因子：
4
作者：
Evdokimov, Evgenij;Sharma, Prashant;Kuehn, Michael R.
通讯作者：
Kuehn, Michael R.
测试报告了大型爱尔兰研究人群中口腔裂口的遗传危险因素的关联。
DOI：
10.1002/bdra.20639
发表时间：
2010-02
影响因子：
--
作者：
Carter, Tonia C.;Molloy, Anne M.;Pangilinan, Faith;Troendle, James F.;Kirke, Peadar N.;Conley, Mary R.;Orr, David J. A.;Earley, Michael;McKiernan, Eamon;Lynn, Ena C.;Doyle, Anne;Scott, John M.;Brody, Lawrence C.;Mills, James L.
通讯作者：
Mills, James L.
影响因子：
64.8
作者：
Basch, ML;Bronner-Fraser, M;García-Castro, MI
通讯作者：
García-Castro, MI