VHL and neoplasm: Some deubiquitinases such as USP8, USP9X, and UCHL1 can participate in VHL-mediated ubiquitination modification of HIF-1α.60, 61, 62 However, under hypoxia, VHL ubiquitination can no longer modify HIF-α (Fig. 2D), which leads to HIF1-α stabilization, thereby mediating vascularization activity and rapid tumor growth.63