Genome-wide analysis of gene expression regulated by APPL1/2 proteins in human PC-3U cells

Transforming growth factor β (TGFβ) is overexpressed in several advanced cancers and promotes tumor progression. How cancer cells evade TGFβ-induced growth inhibition and escape normal homeostasis is unclear. Here, we report that the TGFβ Type I receptor (TβRI), together with the endosomal adaptor proteins APPL1 and APPL2, promote expression of survivin and Aurora kinase B (AURKB). We show that the intracellular part of TβRI binds to AURKB during telophase in PC-3U prostate cancer and KELLY neuroblastoma cells. The TβRI/tumor necrosis factor receptor–associated factor 6 (TRAF6) complex activates AURKB by causing TRAF6-induced Lys63-linked polyubiquitination of AURKB at Lys85 and Lys87, promoting cancer cell division and survival. This mechanism may contribute to the pro-tumorigenic effects of TGFβ in advanced cancers. Total RNA obtained from PC-3U cells in which APPL1 and APPL2 were knocked down by siRNA, compared to the cells which were transfected with control siRNA. Three replicates per group were included.