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The APC-hDLG complex negatively regulates cell cycle progression from the G0/G1 to S phase

Oncogene volume 19, pages 365–372 (2000)Cite this article

Abstract

The adenomatous polyposis coli (APC) gene is mutated in familial adenomatous polyposis and in many sporadic colorectal tumors. The carboxyl-terminal S/TXV motif of the APC gene product interacts with the PDZ domain of hDLG, the human homolog of the Drosophila lethal (1) discs large-1 (dlg) tumor suppressor. In the present study, we found that overexpression of hDLG suppresses cell proliferation by blocking cell cycle progression from the G0/G1 to S phase. This inhibition of cell cycle progression was abolished when the PDZ, SH3 or guanylate kinase-like domain of hDLG was mutated. Moreover, overexpression of these mutant hDLGs partially interfered with the cell cycle blocking activity of APC. Consistent with this result, mutant APC lacking the S/TXV motif exhibited weaker cell cycle blocking activity than the intact APC. These results suggest that APC-hDLG complex formation plays an important role in transducing the APC cell cycle blocking signal.

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Acknowledgements

We thank Y Katoh and A Ogai for technical assistance. This work was supported by Grants-in-Aid from the Ministry of Education, Science and Culture of Japan.

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Authors and Affiliations

  1. Department of Oncogene Research, Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka, 565, Japan

    Takao Ishidate, Akihiko Matsumine & Tetsu Akiyama

  2. Department of Molecular and Genetic Information, Institute for Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113, Japan

    Takao Ishidate & Tetsu Akiyama

  3. Osaka Medical Center for Cancer and Cardiovascular Diseases, Nakamichi, Higashinari-ku, Osaka, Osaka, 537, Japan

    Kumao Toyoshima

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Ishidate, T., Matsumine, A., Toyoshima, K. et al. The APC-hDLG complex negatively regulates cell cycle progression from the G0/G1 to S phase. Oncogene 19, 365–372 (2000). https://doi.org/10.1038/sj.onc.1203309

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