Putative tumor suppressor EDD interacts with and up-regulates APC

Ryuichi Ohshima, Tomohiko Ohta, Wenwen Wu, Ayaka Koike, Tsuguo Iwatani, Michelle Henderson, Colin K.W. Watts, Takehito Otsubo


18 被引用数 (Scopus)


Adenomatous polyposis coli (APC), whose mutation causes colorectal cancers, is a key player in the Wnt signaling pathway. While the role of APC in inhibition of β-catenin/LEF1-dependent activation of transformation-inducing genes has been intensively studied and well established, regulation of APC expression at the protein level is only partially understood. Here we report that APC is up-regulated by EDD, the mammalian orthologue of Drosophila melanogaster "hyperplastic discs" gene (hyd) that is considered to be a putative tumor suppressor. Screening of APC immunocomplexes by mass spectrometry identified EDD as a putative APC-interacting protein. Exogenously expressed and endogenous APC interacted with EDD in vivo. Indirect immunofluorescent analyses demonstrated that APC and EDD co-localized in the cytoplasm of the cell. Over-expression of EDD enhanced the protein expression level of APC and its binding partner Axin, resulting in inhibition of Wnt signaling downstream of β-catenin. Conversely, siRNA knock-down of EDD down-regulated APC at the protein level without altering its mRNA level, causing enhanced protein expression of β-catenin. Thus, through protein-protein interaction, EDD stabilizes APC and up-regulates APC's function to inhibit β-catenin, suggesting that EDD could act as a colorectal tumor suppressor.

ジャーナルGenes to Cells
出版ステータスPublished - 12月 2007

ASJC Scopus subject areas

  • 遺伝学
  • 細胞生物学


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