| 9268294 |
Trzepacz C, Lowy AM, Kordich JJ, Groden J: Phosphorylation of the tumor suppressor adenomatous polyposis coli (APC) by the cyclin-dependent kinase p34. J Biol Chem. 1997 Aug 29;272(35):21681-4.
Mutations in the tumor suppressor gene APC invariably lead to the development of colorectal cancer. The vast majority of these mutations are nonsense or frameshifts resulting in nonfunctional, truncated APC protein products. Eleven cyclin-dependent kinase (CDK) consensus phosphorylation sites have been identified in the frequently deleted carboxyl-terminal region of APC; loss of these phosphorylation sites by mutation could therefore compromise the ability of APC to inhibit cell growth. This report demonstrates that immunoprecipitates of full-length, but not truncated, APC protein include a mitosis-specific kinase activity in vivo. Biochemical and Western analysis of these immunoprecipitates confirms the presence of the CDK p34 (cdc2). We also show that APC is a substrate for recombinant human p34 (cdc2)-cyclin B1. Modification of APC by p34 (cdc2) implicates phosphorylation as a mechanism for regulating APC function via a link to the cell cycle. |
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