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Department of Oncology, The Johns Hopkins University, School of Medicine, Baltimore, Maryland 21231 [L-K. S., B. V., K. W. K.]; Program in Human Genetics, The Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205 [K. J. S., B. V.]; and Oncogene Science, Inc., Cambridge, Massachusetts 02142 [K. A. J., D. E. H.]
Germline mutations of the APC gene are responsible for familial adenomatous polyposis, an autosomal dominant inherited predisposition to colorectal tumors. Mutation of the APC gene is also an early, if not initiating, event for sporadic colorectal tumorigenesis. In both cases, almost all of the currently identified mutations of APC result in the truncation of the protein. In this study, we demonstrate that truncated APC proteins can associate with the wild type APC in vivo. Using in vitro expression and immunoprecipitation, we show that the first 171 residues of APC are sufficient for APC oligomerization and that the first 45 amino acids of APC is necessary for this interaction. These results indicate that most mutant APC proteins should be able to bind to wild type APC protein and perhaps inactivate it in a dominant negative manner.
1 This work was supported in part by grants from the Clayton Fund, McAshan Fund, The Damon Runyon-Walter Winchell Cancer Fund (DRG-1058), and NIH Grants GM-07184 and CA-57345. B. V. is an American Cancer Society Research Professor.
2 To whom requests for reprints should be addressed, at Johns Hopkins Oncology Center, Room 109, 424 North Bond Street, Baltimore, MD 21231.
Received 4/14/93. Accepted 5/11/93.
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