Figure 1
From: Role of Fbxw7 in the maintenance of normal stem cells and cancer-initiating cells
The F-box protein Fbxw7 is required for maintenance of normal stem cells. (A) Fbxw7 is a component of, and responsible for substrate recognition by, an SCF-type ubiquitin ligase. Ubiquitylated substrates are subject to degradation by the proteasome. In the absence of Fbxw7, these substrates accumulate in a manner dependent on cellular context and thereby influence diverse cellular events such as cell cycle progression. (B) Fbxw7 ablation in HSCs results in the accumulation of c-Myc and consequent re-entry of the cells into the cell cycle. The cycling HSCs are then subject to apoptosis as a result of p53 activation, leading to the development of pancytopenia. In the absence of p53 induction, the Fbxw7-deficient HSCs eventually give rise to leukaemia. On the other hand, loss of Fbxw7 in NSCs results in Notch accumulation, with the consequent imbalance between self-renewal and differentiation in these cells, leading to aberrant brain development.
