title: Estramustine-phosphate binds to a tubulin binding domain on microtubule-associated proteins MAP-2 and tau.
abstract: Estramustine-phosphate (EMP), a phosphorylated conjugate of estradiol and nor-nitrogen mustard binds to microtubule-associated proteins MAP-2 and tau. It was shown that this estramustine derivative inhibits the binding of the C-terminal tubulin peptide beta-(422-434) to both MAP-2 and tau. This tubulin segment constitutes a main binding domain for these microtubule-associated proteins. Interestingly, estramustine-phosphate interacted with the synthetic tau peptides V187-G204 and V218-G235, representing two major repeats within the conserved microtubule-binding domain on tau and also on MAP-2. This observation was corroborated by the inhibitory effects of estramustine-phosphate on the tau peptide-induced tubulin assembly into microtubules. On the other hand, the nonphosphorylated drug estramustine failed to block the MAP peptide-induced assembly, indicating that the negatively charged phosphate moiety of estramustine-phosphate is of importance for its inhibitory effect. These findings suggest that the molecular sites for the action of estramustine-phosphate are located within the microtubule binding domains on tau and MAP-2.
authors.affiliation: International Center for Cancer and Developmental Biology (ICC), Santiago Chile.
authors.forename: D
authors.initials: D
authors.lastname: Moraga
authors.forename: A
authors.initials: A
authors.lastname: Rivas-Berrios
authors.forename: G
authors.initials: G
authors.lastname: Farías
authors.forename: M
authors.initials: M
authors.lastname: Wallin
authors.forename: R B
authors.initials: RB
authors.lastname: Maccioni
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D002417:Cattle; D004961:Estramustine / Q000378:metabolism*; D007700:Kinetics; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D014404:Tubulin / Q000378:metabolism*; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D008869:Microtubule-Associated Proteins; D010455:Peptides; D014404:Tubulin; D016875:tau Proteins; D004961:Estramustine