Genome-wide analysis of gene expression regulated by APPL1/2 proteins in human PC-3U cells
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ABSTRACT: 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.
ORGANISM(S): Homo sapiens
PROVIDER: GSE206243 | GEO | 2022/07/16
REPOSITORIES: GEO
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