A DOMAIN WITHIN THE TUMOR-SUPPRESSOR PROTEIN APC SHOWS VERY SIMILAR BIOCHEMICAL-PROPERTIES AS THE MICROTUBULE-ASSOCIATED PROTEIN-TAU

The tumor-suppressor protein APC (adenomatous polyposis coli) binds to microtubules and promotes tubulin assembly. In vivo the endogenous AP C protein is mainly localized at the end of microtubules that are invo lved in active cell migration. Since most tumor-specific APC gene muta tions lead to the loss of the microtubule binding domain this interact ion is assumed to play a crucial role in tumorigenesis. In this study we show that an APC protein fragment (amino acids 2219-2580) within th e C-terminal part is enough to bind to non-assembled tubulin with high affinity. The binding of APC to tubulin does not lead to an alteratio n of the intrinsic GTPase activity of the non-assembled tubulin. The A PC protein induces the tubulin assembly in a fast reaction and below t he critical assembly concentration of tubulin. The APC protein induces the bundling of the assembled microtubules in a concentration-depende nt manner. Regarding its biochemical properties the analysed APC prote in fragment strikingly resembles the members of the microtubule-associ ated protein family tau. This analogy may help to understand the role of the APC protein in the suppression of tumorigenesis.