RNF20 promotes the polyubiquitination and proteasome-dependent degradation of AP-2α protein
RNF20 promotes the polyubiquitination and proteasome-dependent degradation of AP-2α protein
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DOI：
10.1093/abbs/gmt136
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发表时间：
2014-02-01
影响因子：
3.7
通讯作者：
Zhang, Jian
中科院分区：
文献类型：
--
作者：
Ren, Peng;Sheng, Zhifeng;Zhang, Jian
转录因子激活蛋白2（AP-2）通过抑制CCAAT/增强子结合蛋白（C/EBP）基因的转录，是脂肪形成的负调控因子。在脂肪形成过程中，AP-2被降解，导致C/EBP的转录上调。然而，AP-2降解的机制尚不清楚。在这里，使用免疫沉淀分析和质谱，我们确定了环指蛋白20（RNF 20）作为AP-2相互作用的蛋白在3 T3-L1前脂肪细胞。RNF 20是一种E3泛素连接酶，可与组蛋白H2 B和肿瘤抑制因子ErbB 3结合蛋白1（Ebp 1）结合。在这项研究中，我们证明RNF 20与AP-2共定位并相互作用，并促进其多聚泛素化和蛋白酶体依赖性降解。RNF 20的过表达抑制AP-2的活性，并挽救被AP-2抑制的C/EBP表达。这些结果表明RNF 20可能通过刺激AP-2的泛素蛋白酶体依赖性降解而在脂肪细胞分化中发挥作用。
Transcription factor activator protein 2 (AP-2) is a negative regulator of adipogenesis by repressing the transcription of CCAAT/enhancer binding protein (C/EBP) gene. During adipogenesis, AP-2 is degraded, leading to transcriptional up-regulation of C/EBP. However, the mechanism for AP-2 degradation is not clear. Here, using immunoprecipitation assay and mass spectrometry, we identified ring finger protein 20 (RNF20) as an AP-2-interacting protein in 3T3-L1 preadipocytes. RNF20 has been proved to be an E3 ubiquitin ligase for both histone H2B and tumor suppressor ErbB3-binding protein 1 (Ebp1). In this study, we demonstrated that RNF20 co-localized and interacted with AP-2, and promoted its polyubiquitination and proteasome-dependent degradation. Over-expression of RNF20 inhibited the activity of AP-2 and rescued the C/EBP expression which was inhibited by AP-2. These results suggested that RNF20 may play roles in adipocyte differentiation by stimulating ubiquitinproteasome-dependent degradation of AP-2.