Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences & Comparative Medical Center, Peking Union Medical College, Beijing, China.
Beijing Ditan Hospital, Capital Medical University, Beijing, China.
Cell Signal. 2017 Oct;38:60-66. doi: 10.1016/j.cellsig.2017.06.010. Epub 2017 Jun 27.
The HECT E3 ligase Smurf1 (Smad ubiquitination regulatory factor 1) plays a critical role in several important biological pathways by targeting many proteins for ubiquitination and degradation, such as Smad1/5, MEKK2 and RhoA. However, the function of Smurf1 in metaphase-to-anaphase transition remains unclear. Here, we show that Smurf1 interacts with and targets Securin, an inhibitor of sister-chromatid separation, for poly-ubiquitination and proteasomal degradation. Further results demonstrate that Securin is a physiological substrate of Smurf1 in MEF cells. Knockdown of Smurf1 results in sister-chromatid separation inhibition and delay of anaphase onset. This study provides the first evidence that Smurf1 functions as a novel regulator for the metaphase-to-anaphase transition.
HECT E3 连接酶 Smurf1（Smad 泛素化调节因子 1）通过靶向许多蛋白质进行泛素化和降解，在几种重要的生物学途径中发挥关键作用，如 Smad1/5、MEKK2 和 RhoA。然而，Smurf1 在中期到后期过渡中的功能尚不清楚。在这里，我们表明 Smurf1 与姐妹染色单体分离抑制剂 Securin 相互作用，并将其靶向进行多泛素化和蛋白酶体降解。进一步的结果表明，Securin 是 MEF 细胞中 Smurf1 的生理底物。Smurf1 的敲低导致姐妹染色单体分离抑制和后期起始延迟。这项研究首次提供证据表明 Smurf1 作为中期到后期过渡的新型调节剂发挥作用。
