Estramustine-phosphate binds to a tubulin binding domain on microtubule-associated proteins MAP-2 and tau.
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.
Moraga
D
D
International Center for Cancer and Developmental Biology (ICC), Santiago Chile.
Rivas-Berrios
A
A
Farías
G
G
Wallin
M
M
Maccioni
R B
RB
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
D008869:Microtubule-Associated Proteins; D010455:Peptides; D014404:Tubulin; D016875:tau Proteins; D004961:Estramustine