Biomaterial Database

Interactions of the tau-tubulin-vinblastine complex with colchicine, podophyllotoxin, and N,N'-ethylenebis(iodoacetamide). 1982

P Palanivelu, and R F Ludueña

Microtubule assembly is inhibited by anti-mitotic drugs such as colchicine or podophyllotoxin and also by sulfhydryl-oxidizing reagents, but it is not known which tubulin-tubulin interactions are disrupted by these agents. We have studied the interactions of a complex of tubulin, vinblastine, and tau protein with these agents. This complex has the form of a spiral filament and may consist of tubulin dimers joined end to end as in a protofilament; presumably, therefore, the lateral interaction sites should be accessible in this structure but not in the intact microtubule. Unlike the microtubule, the complex binds to colchicine and podophyllotoxin with high affinity. Again, unlike intact microtubules, the complex reacts with N,N'-ethylene-bis(iodoacetamide) to generate an intra-chain cross-link in beta-tubulin. Tubulin molecules containing this cross-link are unable to polymerize, suggesting that formation of this cross-link involves sulfhydryl groups that are critical for assembly. These results are consistent with a model whereby colchicine-, podophyllotoxin-, and sulfhydryl-oxidizing agents inhibit microtubule assembly by preventing lateral interactions between tubulin molecules in adjacent protofilaments.

UI	MeSH Term	Description	Entries
D007460	Iodoacetamide	An alkylating sulfhydryl reagent. Its actions are similar to those of iodoacetate.
D007461	Iodoacetates	Iodinated derivatives of acetic acid. Iodoacetates are commonly used as alkylating sulfhydryl reagents and enzyme inhibitors in biochemical research.	Iodoacetic Acids,Acids, Iodoacetic
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008870	Microtubules	Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein TUBULIN and are influenced by TUBULIN MODULATORS.	Microtubule
D009419	Nerve Tissue Proteins		Proteins, Nerve Tissue,Tissue Proteins, Nerve
D011034	Podophyllotoxin	A lignan (LIGNANS) found in PODOPHYLLIN resin from the roots of PODOPHYLLUM plants. It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives.	Epipodophyllotoxin,CPH86,Condyline,Condylox,Podocon-25,Podofilm,Podofilox,Podophyllotoxin, (5R-(5 alpha,5a alpha,8a alpha,9 alpha))-Isomer,Podophyllotoxin, (5R-(5 alpha,5a alpha,8a alpha,9 beta))-Isomer,Podophyllotoxin, (5R-(5 alpha,5a alpha,8a beta,9 alpha))-Isomer,Podophyllotoxin, (5R-(5 alpha,5a beta,8a alpha,9 beta))-Isomer,Wartec,Warticon
D011506	Proteins	Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.	Gene Products, Protein,Gene Proteins,Protein,Protein Gene Products,Proteins, Gene
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D002417	Cattle	Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.	Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D003078	Colchicine	A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (PERIODIC DISEASE).	Colchicine, (+-)-Isomer,Colchicine, (R)-Isomer