F-box protein FBXO22 mediates polyubiquitination and degradation of KLF4 to promote hepatocellular carcinoma progression
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Xin Tian1, Shundong Dai2,3, Jing Sun4, Guojiang Jin5, Shenyi Jiang6, Fandong Meng1, Yan Li1, Di Wu1, Youhong Jiang1
1Molecular Oncology Laboratory of Cancer Research Institute, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China
2Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, 110001, China
3Institute of Pathology and Pathophysiology, Shenyang, 110001, China
4Department of Immunology and Biotherapy, Liaoning Cancer Hospital and Institute, Shenyang, 110042, China
5Department of Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China
6Department of Rheumatology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China
Youhong Jiang, e-mail: firstname.lastname@example.org
Keywords: Kruppel-like factor 4, FBXO22, hepatocellular carcinoma, ubiquitination
Received: March 21, 2015 Accepted: May 14, 2015 Published: May 28, 2015
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.
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