Microtubules activity

The cytosolic dyneins bear many similarities to axonemal dynein. The protein isolated from C. elegans includes a heavy chain with a molecular mass of approximately 400 kD, as well as smaller peptides with molecular mass ranging from 53 kD to 74 kD. The protein possesses a microtubule-activated ATPase... 

Both dynein and MAP2 interact with microtubules at the same binding sites, namely, the C termini of a- and p-tubulin. Also, MAP2 inhibits the microtubule-activated ATPase of dynein and prevents microtubule gliding on dynein-coated glass coverslips. Thus, MAP2 and other fibrous MAPs may be regulators of microtubule-based motility in vivo (Paschal et al., 1989). 

Paschal, B.M., Shpetner, H.S., Vallee, R.B. (1987). MAP IC is a microtubule-activated ATPase which translocates microtubules in vitro and has dynein-like properties. J. Cell Biol. 105, 1273-1282. 

Tubulin/Microtubule activities" Activities with cultured ceils h... 

Das KC, Guo X, White CW (1998) Protein kinase C8-dependent induction of Manganese superoxide dismutase gene e q>ression by microtubule-active anticancer drugs. J Biol Chem 273 34639-34645... 

Zhang C. Genetic susceptibility to microtubule-active cancer chemotherapeutic drugs p53 action and the role of MAP4. Proceedings ofAACR 1998 1308. 

Morejohn LC, Fosket OE. The biochemistry of compounds with anti-microtubule activity in plant cells. Phatmacol Ther 1991 51 217-230. 

Y. V. Evtodienko, V. V. Teplova, S. S. Sidash, F. Ichas, and J. P. Mazat, Microtubule-active drags suppress the closure of the permeability transition pore in tumour mitochondria. FEBSLett., 393 (1996) 86-8. 

Synthesis and biological evaluation as microtubule-active agents of several tetrahydrofiiran and spiroacetal derivatives 13CMD1173. Tandem multicomponent reactions toward the des p and synthesis of novel polysubstituted imidazopyridines and imidazopyrazines as antibacterial and cytotoxic motifs 13CMD1445. 

Kobayashi, H., Meguro, S., Yoshimoto, T, and Namikoshi, M. (2003) Absolute structure, biosynthesis, and anti-microtubule activity of phomopsidin, isolated from a marine-derived fungus Phomopsis sp. Tetrahedron, 59, 455—459. Corrigendum Tetrahedron, 60,1255 (2004). 

Vinca alkaloids (vincristine, vinblastine, vindesine) are derived from the periwinkle plant (Vinca rosea), they bind to tubulin and inhibit its polymerization into microtubules and spindle formation, thus producing metaphase arrest. They are cell cycle specific and interfere also with other cellular activities that involve microtubules, such as leukocyte phagocytosis, chemotaxis, and axonal transport in neurons. Vincristine is mainly neurotoxic and mildly hematotoxic, vinblastine is myelosuppressive with veiy low neurotoxicity whereas vindesine has both, moderate myelotoxicity and neurotoxicity. 

MAP is the acronym for both, Microtubule Associated Protein and Mitogen Activated Protein. 

A signal transduction pathway required for proper chromosome alignment during mitosis. The spindle assembly checkpoint is activated during mitosis in response to the presence of chromosomes that are not attached to spindle microtubules or that are not properly aligned at the metaphase plate. The spindle checkpoint... 

Vinca alkaloids are derived from the Madagascar periwinkle plant, Catharanthus roseus. The main alkaloids are vincristine, vinblastine and vindesine. Vinca alkaloids are cell-cycle-specific agents and block cells in mitosis. This cellular activity is due to their ability to bind specifically to tubulin and to block the ability of the protein to polymerize into microtubules. This prevents spindle formation in mitosing cells and causes arrest at metaphase. Vinca alkaloids also inhibit other cellular activities that involve microtubules, such as leukocyte phagocytosis and chemotaxis as well as axonal transport in neurons. Side effects of the vinca alkaloids such as their neurotoxicity may be due to disruption of these functions. 

An isolated flagellum will continue to bend actively, indicating that this function is linked to its intrinsic structure. Treatment of cilia from the protozoan Tetra-hymena with the proteolytic enzyme trypsin selectively dissolves the nexin links and radial spokes but leaves unaffected the microtubules and dynein arms. If such a preparation is treated with a small amount of ATP, the loosened microtubule doublets slide against each other and through longitudinal overlap, extend for a distance that is up to nine times the original length of the cilium (Warner and Mitchell, 1981). 

Just as myosins are able to move along microfilaments, there are motor proteins that move along microtubules. Microtubules, like microfilaments, are polar polymeric assemblies, but unlike actin-myosin interactions, microtubule-based motors exist that move along microtubules in either direction. A constant traffic of vesicles and organelles is visible in cultured cells especially using time-lapse photography. The larger part of this movement takes place on micrombules and is stimulated by phorbol ester (an activator of protein kinase C), and over-expression of N-J aj oncoprotein (Alexandrova et al., 1993). 

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