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Effect of estramustine phosphate on the assembly of trypsin-treated microtubules and microtubules reconstituted from purified tubulin with either tau, MAP2, or the tubulin-binding fragment of MAP2.
- Source :
-
Archives of biochemistry and biophysics [Arch Biochem Biophys] 1987 Aug 15; Vol. 257 (1), pp. 123-30. - Publication Year :
- 1987
-
Abstract
- Estramustine phosphate, an estradiol nitrogen-mustard derivative is a microtubule-associated protein (MAP)-binding microtubule inhibitor, used in the therapy of prostatic carcinoma. It was found to inhibit assembly and to induce disassembly of microtubules reconstituted from phosphocellulose-purified tubulin with either tau, microtubule-associated protein 2, or chymotrypsin-digested microtubule-associated protein 2. Estramustine phosphate also inhibited assembly of trypsin-treated microtubules, completely depleted of high-molecular-weight microtubule-associated proteins, but with their microtubule-binding fragment present. In all cases estramustine phosphate induced disassembly to about 50%, at a concentration of approximately 100 microM, at similar protein concentrations. However, estramustine phosphate did not affect dimethyl sulfoxide-induced assembly of phosphocellulose-purified tubulin. Estramustine phosphate is a reversible inhibitor, as the nonionic detergent Triton X-100 was found to counteract the inhibition in a concentration-dependent manner. The reversibility was nondisruptive, as Triton X-100 itself did not affect microtubule assembly, microtubule protein composition, or morphology. This new reversible MAPs-dependent inhibitor estramustine phosphate affects the tubulin assembly, induced by tau, as well as by the small tubulin-binding part of MAP2 with the same concentration dependency. This indicates that tau and the tubulin-binding part of MAP2, in addition to their assembly promoting functions also have binding site(s) for estramustine phosphate in common.
- Subjects :
- Binding Sites
Estramustine metabolism
Microtubules metabolism
Octoxynol
Polyethylene Glycols pharmacology
tau Proteins
Estramustine pharmacology
Microtubule-Associated Proteins metabolism
Microtubules drug effects
Nitrogen Mustard Compounds pharmacology
Peptide Fragments metabolism
Trypsin pharmacology
Tubulin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0003-9861
- Volume :
- 257
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Archives of biochemistry and biophysics
- Publication Type :
- Academic Journal
- Accession number :
- 3115177
- Full Text :
- https://doi.org/10.1016/0003-9861(87)90550-9