title: Emerging roles of the FBW7 tumour suppressor in stem cell differentiation.
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.
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Wang
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Inuzuka
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Fukushima
authors.forename: Lixin
authors.initials: L
authors.lastname: Wan
authors.forename: Daming
authors.initials: D
authors.lastname: Gao
authors.forename: Shavali
authors.initials: S
authors.lastname: Shaik
authors.forename: Fazlul H
authors.initials: FH
authors.lastname: Sarkar
authors.forename: Wenyi
authors.initials: W
authors.lastname: Wei
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D058990:Molecular Targeted Therapy; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: D044783:F-Box Proteins; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases