In addition to proteins known to directly bind REN, such as Cul3, RBX1, and KCTD15 (Supplementary Fig. 2A) [6, 27], we recovered various potential REN interactors (Fig. 1B) including SALL4, a cell stemness regulator aberrantly activated in several types of human cancers [18–24]. Here, CUL3 is linked to cancer.