SCF^<Fbxl12>modulates the abundance of p21 in concert with proteasome activator PA28γ

泛素-蛋白酶体系统（UPS）在细胞周期调控和DNA损伤反应中起重要作用。SCF复合物是控制这些过程的主要泛素连接酶。本研究发现，SCF_<Fbxl12>（1-x）与蛋白酶体亚基PA 28 γ和细胞周期蛋白依赖性激酶（cyclin-dependent kinase，CDK）抑制剂p21结合，参与细胞内p21丰度的调节。此外，这种复合物形成能力被UV刺激减弱。我们还发现，Fbxl 12的内含子区域作为一个替代的启动子，并诱导响应于紫外线照射的Fbxl 12的短形式的表达。综上所述，这些数据表明，Fbxl 12是一个关键的调解人，链接紫外线照射p21降解，和Fbxl 12的这种新的功能可能会提供一个深入了解DNA损伤介导的p21稳定的机制。

The ubiquitin-proteasome system (UPS) plays an important role for the regulation of cell cycle and DNA damage response. The SCF complexes are the major ubiquitin ligases that control these processes. In this study, we found that SCF^<Fbxl12>associates with proteasomal subunit PA28γ and cyclin-dependent kinase (CDK) inhibitor p21, and is involved in the regulation of p21 abundance in cell. In addition, this complex-forming ability is attenuated by UV stimulation. We also found that the intronic regions of Fbxl12 acts as an alternative promoter and induces expression of short form of Fbxl12 in response to UV irradiation. Taken together, these data demonstrate that Fbxl12 is a key mediator that links UV irradiation to p21 degradation, and this novel function of Fbxl12 may provide an insight into the mechanisms by which DNA damage mediates p21 stabilization.