FBW7-mediated ubiquitination and degradation of KLF5

• 作者: Ping Wang Yi Luan
• 来源期刊: 世界生物化学杂志：英文版（电子版）
• 学科: 医学
• 关键词: Krüppel-like FACTOR 5 FBW7 Ubiquitin PROTEASOME system DEGRADATION Krüppel-like FACTOR family
• 年，卷（期）: 2014,（2）
• 页码范围: 216-223
• 页数: 8页
• 分类号: R3411

摘要

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 mousemodels, 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.