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 APC protein is mainly localized at the end of microtubules that are involved in active cell migration. Since most tumor-specific APC gene mutations lead to the loss of the microtubule binding domain this interaction is assumed to play a crucial role in tumorigenesis. In this study we show that an APC protein fragment (amino acids 2219-2580) within the 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 alteration of the intrinsic GTPase activity of the non-assembled tubulin. The APC protein induces the tubulin assembly in a fast reaction and below the critical assembly concentration of tubulin. The APC protein induces the bundling of the assembled microtubules in a concentration-dependent manner. Regarding its biochemical properties the analysed APC protein fragment strikingly resembles the members of the microtubule-associated protein family tau. This analogy may help to understand the role of the APC protein in the suppression of tumorigenesis.
Deka
J
J
Arbeitsgruppe Tumorgenetik, Abteilung Strukturelle Biologie, Max-Planck-Institut für molekulare Physiologie, Dortmund, Germany.
Kuhlmann
J
J
Müller
O
O
D025601:Adenomatous Polyposis Coli Protein; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D002942:Circular Dichroism; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins / Q000737:chemistry* / Q000378:metabolism; D019281:Dimerization; D020558:GTP Phosphohydrolases / Q000378:metabolism; D017491:Genes, APC; D006801:Humans; D007700:Kinetics; D008870:Microtubules / Q000648:ultrastructure; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism; D016875:tau Proteins / Q000737:chemistry*
D025601:Adenomatous Polyposis Coli Protein; D003598:Cytoskeletal Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D014404:Tubulin; D016875:tau Proteins; D020558:GTP Phosphohydrolases