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

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1339-1345
Number of pages7
JournalGenes to Cells
Volume12
Issue number12
DOIs
Publication statusPublished - Dec 2007
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Fingerprint

Dive into the research topics of 'Putative tumor suppressor EDD interacts with and up-regulates APC'. Together they form a unique fingerprint.

Cite this