F-box protein FBXO22 mediates polyubiquitination and degradation of KLF4 to promote hepatocellular carcinoma progression.
F-box protein FBXO22 mediates polyubiquitination and degradation of KLF4 to promote hepatocellular carcinoma progression.
复制标题
F-box蛋白FBXO22介导KLF4多聚泛素化和降解促进肝细胞癌进展
DOI：
10.18632/oncotarget.4082
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发表时间：
2015-09-08
期刊：
影响因子：
--
通讯作者：
Jiang Y
中科院分区：
文献类型：
--
作者：
Tian X;Dai S;Sun J;Jin G;Jiang S;Meng F;Li Y;Wu D;Jiang Y
Kruppel样因子4（KLF 4）是KLF家族转录因子中的一员，被认为是肝细胞癌（HCC）的重要抑癌因子。利用亲和纯化和质谱分析，我们确定FBXO 22，Cullin 1和SKP 1为KLF 4的相互作用蛋白。我们证明了F-box only蛋白22（FBXO 22）与KLF 4相互作用，从而通过多聚泛素化使KLF 4不稳定。结果表明，FBXO 22在体内外均能促进肝癌细胞增殖。然而，KLF 4缺陷在很大程度上阻断了FBXO 22的增殖作用。重要的是，FBXO 22在人HCC组织中的表达显著增加，这与KLF 4的下调相关。因此，我们的研究结果表明，FBXO 22可能是通过直接降解KLF 4的HCC发展的主要调节剂。
Kruppel-like factor 4 (KLF4), a member of the KLF family of transcription factors, has been considered as a crucial tumor suppressor in hepatocellular carcinoma (HCC). Using affinity purifications and mass spectrometry, we identified FBXO22, Cullin1 and SKP1 as interacting proteins of KLF4. We demonstrate that F-box only protein 22 (FBXO22) interacts with and thereby destabilizes KLF4 via polyubiquitination. As a result, FBXO22 could promote HCC cells proliferation both in vitro and in vivo. However, KLF4 deficiency largely blocked the proliferative roles of FBXO22. Importantly, FBXO22 expression was markedly increased in human HCC tissues, which was correlated with down-regulation of KLF4. Therefore, our results suggest that FBXO22 might be a major regulator of HCC development through direct degradation of KLF4.