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- Title
Human scribble, a novel tumor suppressor identified as a target of high-risk HPV E6 for ubiquitin-mediated degradation, interacts with adenomatous polyposis coli.
- Authors
Takizawa, Shin; Nagasaka, Kazunori; Nakagawa, Shunsuke; Yano, Tetsu; Nakagawa, Keiichi; Yasugi, Toshiharu; Takeuchi, Takamasa; Kanda, Tadahito; Huibregtse, Jon M.; Akiyama, Tetsu; Taketani, Yuji
- Abstract
Recently, we have identified human scribble (hScrib), human homolog of the Drosophila tumor suppressor Scribble, as a substrate of human papillomavirus E6 oncoproteins for ubiquitin-mediated degradation dependent on ubiquitin-protein ligase E6AP. Human Scribble, classified as a LAP protein containing eucine-rich repeats nd DZ domains, interacts with E6 through its PDZ domains and C-terminal PDZ domain-binding motif of E6 protein. Interaction between human Discs Large (hDlg), which is a substrate of E6 for the ubiquitin-mediated degradation, and adenomatous polyposis coli (APC) has been shown. Here, we investigated whether hScrib and APC interact with each other in vitro and in vivo. Interaction between hScrib and APC is mediated by the PDZ domains 1 and 4 of hScrib and C-terminal PDZ domain-binding motif of APC. Human Scribble co-localized with APC at the synaptic sites of hippocampal neuron and at the tip of membrane protrusion in the epithelial cell line. Interference of the interaction between hScrib and APC caused disruption of adherens junction. Knockdown of hScrib expression by RNAi disrupts localization of APC at the adherens junction. These data suggest that hScrib may participate in the hDlg-APC complex through its PDZ domains and regulate cell cycle and neural function by associating with APC.
- Subjects
PROTEINS; DROSOPHILA; TUMORS; PAPILLOMAVIRUSES; EPITHELIAL cells; CELLS; FRUIT flies
- Publication
Genes to Cells, 2006, Vol 11, Issue 4, p453
- ISSN
1356-9597
- Publication type
Article
- DOI
10.1111/j.1365-2443.2006.00954.x