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Ishidate, T, Matsumine, A, Toyoshima, K and Akiyama, T (2000) The APC-hDLG complex negatively regulates cell cycle progression from the G0/G1 to S phase. Oncogene 19:365-72


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.


PubMed Online version:10.1038/sj.onc.1203309


3T3 Cells; Animals; COS Cells; Cell Cycle; Drosophila Proteins; G0 Phase; G1 Phase; Genes, APC/physiology; Genes, Tumor Suppressor; Guanylate Kinase; Humans; Insect Proteins/physiology; Mice; Nucleoside-Phosphate Kinase/chemistry; Nucleoside-Phosphate Kinase/physiology; S Phase; Tumor Suppressor Proteins; src Homology Domains