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

泛素-蛋白酶体系统（UPS）在细胞周期和DNA损伤反应的调控中起着重要作用。SCF复合物是控制这些过程的主要泛素连接酶。在本研究中，我们发现SCF^<Fbxl12>与蛋白酶体亚基PA28γ和细胞周期蛋白依赖性激酶（CDK）抑制剂p21相关，并参与细胞中p21丰度的调控。此外，这种络合物形成能力被紫外线刺激减弱。我们还发现Fbxl12的内含子区作为替代启动子，诱导短形式Fbxl12在紫外线照射下的表达。综上所述，这些数据表明Fbxl12是将紫外线照射与p21降解联系起来的关键介质，Fbxl12的这种新功能可能为DNA损伤介导p21稳定的机制提供了新的见解。

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.