Emerging roles of the FBW7 tumour suppressor in stem cell differentiation

Zhiwei Wang, Hiroyuki Inuzuka, Hidefumi Fukushima, Lixin Wan, Daming Gao, Shavali Shaik, Fazlul H. Sarkar, Wenyi Wei

Research output: Contribution to journalReview articlepeer-review

45 Citations (Scopus)

Abstract

FBW7 is a ubiquitin E3 ligase substrate adaptor that targets many important oncoproteins-such as Notch, c-Myc, cyclin E and c-Jun-for ubiquitin-dependent proteolysis. By doing so, it plays crucial roles in many cellular processes, including cell cycle progression, cell growth, cellular metabolism, differentiation and apoptosis. Loss of FBW7 has been observed in many types of human cancer, and its role as a tumour suppressor was confirmed by genetic ablation of FBW7 in mice, which leads to the induction of tumorigenesis. How FBW7 exerts its tumour suppression function, and whether loss of FBW7 leads to de-differentiation or acquisition of stemness-a process frequently seen in human carcinomas-remains unclear. Emerging evidence shows that FBW7 controls stem cell self-renewal, differentiation, survival and multipotency in various stem cells, including those of the haematopoietic and nervous systems, liver and intestine. Here, we focus on the function of FBW7 in stem cell differentiation, and its potential relevance to human disease and therapeutics.

Original languageEnglish
Pages (from-to)36-43
Number of pages8
JournalEMBO Reports
Volume13
Issue number1
DOIs
Publication statusPublished - 2012 Jan

Keywords

  • FBW7
  • Notch
  • c-Jun
  • differentiation
  • stem cell

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

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