WSB2 and colonic neoplasm: To determine the effects of these E3 ligases on protein levels of endogenous cyclin D1, we transfected Keap1, DDB2, WSB2, and Rbx1 siRNA into human colon cancer cell line HCT-116 cells and found that knocking down of Keap1, DDB2, WSB2, or Rbx1 significantly enhanced endogenous cyclin D1 protein levels (Figure 2A, D, G, and J).