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World J Biol Chem. May 26, 2014; 5(2): 216-223
Published online May 26, 2014. doi: 10.4331/wjbc.v5.i2.216
FBW7-mediated ubiquitination and degradation of KLF5
Yi Luan, Ping Wang
Yi Luan, Ping Wang, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China
Author contributions: Luan Y and Wang P contributed equally to this paper.
Supported by Grants from National Basic Research Program of China, 973 program, No. 2010CB529704 and No. 2012CB910404; National Natural Science Foundation of China, No. 30800587, No. 30971521, and No. 31171338; and the Science and Technology Commission of Shanghai Municipality, No. 11DZ2260300; a scholar of the Shanghai Rising-Star Program from Science and Technology Commission of Shanghai Municipality, No. 09QA1401900 to Wang P
Correspondence to: Ping Wang, PhD, Professor, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China. pwang@bio.ecnu.edu.c
Telephone: +86-21-54345021 Fax: +86-21-54344922
Received: November 14, 2013
Revised: January 15, 2014
Accepted: March 17, 2014
Published online: May 26, 2014
Processing time: 208 Days and 17.4 Hours
Abstract

Krüppel-like factor (KLF) family proteins are transcription factors that regulate numerous cellular functions, such as cell proliferation, differentiation, and cell death. Posttranslational modification of KLF proteins is important for their transcriptional activities and biological functions. One KLF family member with important roles in cell proliferation and tumorigenesis is KLF5. The function of KLF5 is tightly controlled by post-translational modifications, including SUMOylation, phosphorylation, and ubiquitination. Recent studies from our lab and others’ have demonstrated that the tumor suppressor FBW7 is an essential E3 ubiquitin ligase that targets KLF5 for ubiquitination and degradation. KLF5 contains functional Cdc4 phospho-degrons (CPDs), which are required for its interaction with FBW7. Mutation of CPDs in KLF5 blocks the ubiquitination and degradation of KLF5 by FBW7. The protein kinase Glycogen synthase kinase 3β is involved in the phosphorylation of KLF5 CPDs. In both cancer cell lines and mouse models, it has been shown that FBW7 regulates the expression of KLF5 target genes through the modulation of KLF5 stability. In this review, we summarize the current progress on delineating FBW7-mediated KLF5 ubiquitination and degradation.

Keywords: Krüppel-like factor 5; FBW7; Ubiquitin proteasome system; Degradation; Krüppel-like factor family

Core tip: The protein levels of Krüppel-like factor (KLF)5 are tightly controlled in cell. Ubiquitination and destruction of KLF5 via FBW7, a famous tumor suppressor, has proved to have important roles in multiple cellular progresses by different studies. Here, we summarize these studies and show the physiological and pathological significance of FBW7-mediated degradation of KLF5.