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Oncogene. 2000 Jan 20;19(3):365-72.

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

Author information

1
Department of Oncogene Research, Institute for Microbial Diseases, Osaka University, Suita, Japan.

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 larige-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.

PMID:
10656683
DOI:
10.1038/sj.onc.1203309
[Indexed for MEDLINE]
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