One study showed that extracellular signal-regulated kinase (ERK) directly interacted with and phosphorylated FBXW7 at Thr205, which promoted FBXW7 ubiquitylation in a PIN-1 dependent manner in pancreatic cancer cells, although exactly how ERK-mediated FBXW7 phosphorylation triggers FBXW7 ubiquitylation remains elusive (Ji et al., 2015). Here, FBXW7 is linked to familial pancreatic carcinoma.