Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10636 (tau protein)
 5,110 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

AIM:To investigate the interaction of Zot with microtubule.METHODS:Zot affinity column was applied to purify Zot-binding protein(s) from crude intestinal cell lysates. After incubation at room temperature, the column was washed and the proteins bound to the Zot affinity column were eluted by step gradient with NaCl (0.3molcenter dotL(-1) -0.5molcenter dotL(-1)). The fractions were subjected to 6.0%-15.0% (w/v) gradient SDS-PAGE and then transferred to PVDF membrane for N-terminal sequencing.Purified Zot and tau protein were blotted by using anti-Zot or anti tau antibodies. Finally, purified Zot was tested in an in vitro tubulin binding assay.RESULTS:Fractions from Zot affinity column yielded two protein bands with a M(r) of 60kU and 45kU respectively. The Nterminal sequence of the 60kU band resulted identical to beta-tubulin. Zot also crossreacts with antitau antibodies. In the in vitro tubulin binding assay, Zot coprecipitate with Mt, further suggesting that Zot possesses tubulin-binding properties.CONCLUSION:Taken together, these results suggest that Zot regulates the permeability of intestinal tight junctions by binding to intracellular Mt, with the subsequent activation of the intracellular signaling leading to the permeabilization of intercellular tight junctions.
 ...
PMID:Zonula occludin toxin, a microtubule binding protein. 1181 91

We investigated whether discodermolide, a novel antimitotic agent, affects the binding to microtubules of tau protein repeat motifs. Like taxol, the new drug reduces the proportion of tau that pellets with microtubules. Despite their differing structures, discodermolide, taxol and tau repeats all bind to a site on beta-tubulin that lies within the microtubule lumen and is crucial in controlling microtubule assembly. Low concentrations of tau still bind strongly to the outer surfaces of preformed microtubules when the acidic C-terminal regions of at least six tubulin dimers are available for interaction with each tau molecule; otherwise binding is very weak.
 ...
PMID:Discodermolide interferes with the binding of tau protein to microtubules. 1265 Sep 22

Microtubules are designed to be dynamically unstable. GTP hydrolysis converts an initially stable polymeric structure into an unstable one in which strain at the interfaces between longitudinal neighbours in the helical lattice of subunits is balanced by lateral interactions. However, stability can be modulated by a variety of factors, including associated proteins and a variety of drug molecules. Stabilising drugs such as Taxol and the assembly-promoting repeat motifs of tau protein occupy a special pocket in beta-tubulin. Microtubule destabilizing drugs such as colchicine alter the longitudinal interfaces of the subunits so that they cannot assemble into a microtubule lattice. These mechanisms are discussed in terms of the atomic structure of the protein.
 ...
PMID:Microtubule structure and its stabilisation. 1528 Sep 46

This paper discusses the results of homology modeling and resulting calculation of key structural and physical properties for close to 300 tubulin sequences, including alpha, beta, gamma, delta and epsilon -tubulins. The basis for our calculations was the structure of the tubulin dimer published several years ago by Nogales et al. (1998), later refined to 3.5 resolution by Lowe et al. (2001). While, it appears that the alpha, beta and gamma-tubulins segregate into distinct structural families, we have found several differences in the physical properties within each group. Each of the alpha, beta and gamma- tubulin groups exhibit major differences in their net electric charge, dipole moments and dipole vector orientations. These properties could influence functional characteristics such as microtubule stability and assembly kinetics, due to their effects on the strength of protein-protein interactions. In addition to the general structural trends between tubulin isoforms, we have observed that the carboxy-termini of alpha and beta-tubulin exists in at least two stable configurations, either projecting away from the tubulin (or microtubule) surface, or collapsed onto the surface. In the latter case, the carboxy-termini form a lattice distinctly different from that of the well-known A and B lattices formed by the tubulin subunits. However, this C-terminal lattice is indistinguishable from the lattice formed when the microtubule-associated protein tau binds to the microtubule surface. Finally, we have discussed how tubulin sequence diversity arose in evolution giving rise to its particular phylogeny and how it may be used in cell- and tissue-specific expression including embryonal development.
 ...
PMID:The evolution of the structure of tubulin and its potential consequences for the role and function of microtubules in cells and embryos. 1647 2

The synthesis of a series of novel docetaxel analogues possessing a peptide side chain at the C2 position as well as peptide macrocyclic taxoids is described. These compounds were designed to mimic a region of the alpha-tubulin loop equivalent to the paclitaxel binding pocket of beta-tubulin. Fifteen new peptide taxoids were obtained and evaluated as inhibitors of microtubule disassembly as well as cell proliferation. The relationships between these new taxoids and the tau protein motif interacting with microtubules are discussed.
 ...
PMID:Novel C2-C3' N-peptide linked macrocyclic taxoids. Part 2: synthesis and biological activities of docetaxel analogues with a peptide side chain at C2 and their macrocyclic derivatives. 1706 14

Taxanes (e.g. paclitaxel, docetaxel) and epothilones (e.g. ixabepilone) are microtubule-targeting agents, which disrupt cellular processes and induce apoptosis. Although their mechanisms of action are similar, clinical data in breast cancer patients support at least partial non-cross resistance between the classes, and even between individual compounds. Several biomarkers might contribute to the identification of patient groups likely to derive benefit from one class of microtubule-targeting agent or even one agent. Overexpression of P-glycoprotein is associated with resistance to taxanes, but not ixabepilone, in vitro; its role in vivo remains unclear. Mutations in beta-tubulin linked to resistance to taxanes but not epothilones are observed in vitro; somatic mutations of beta-tubulin appear rare clinically. Overexpression of the betaIII-tubulin isoform is associated with taxane resistance in cell lines; some clinical studies support a relationship between poor response to taxanes and overexpression of betaIII-tubulin. BetaIII-tubulin overexpression seems not to affect sensitivity to ixabepilone. Estrogen receptor negativity, low expression of microtubule-associated protein tau, and perhaps HER2 amplification may define a subset of patients with higher than average sensitivity to paclitaxel. Large scale pharmacogenomic analysis has identified molecular markers potentially capable of distinguishing patients with differential sensitivity to paclitaxel and ixabepilone. These markers require validation in clinical trials.
 ...
PMID:Markers predicting clinical benefit in breast cancer from microtubule-targeting agents. 1808 98

Pineal parenchymal tumor (PPT) cells usually show immunoreactivity for synaptophysin, neuron-specific enolase, neurofilament protein, class III beta-tubulin, tau protein, PGP9.5, chromogranin, serotonin, retinal S-antigen, and rhodopsin, but these markers are not specific for PPTs. Melatonin is produced and secreted mainly bypineal parenchymal cells; hydroxyindole-O-methyltransferase (HIOMT) catalyzes the final reaction in melatonin biosynthesis. We hypothesized that HIOMT could serve as a tumor marker of PPTs, and we investigated HIOMT localization and HIOMT expression in samples of normal human tissue and in PPTs, primitive neuroectodermal tumors, and medulloblastomas. In normal tissue, HIOMT was expressed in retinal cells, pineal parenchymal cells, neurons of the Edinger-Westphal nucleus, microglia, macrophages, thyroid follicular epithelium, principal and oxyphil cells of parathyroid gland, adrenal cortical cells, hepatic parenchymal cells, renal tubule epithelium, and enteroendocrine cells of stomach and duodenum. The HIOMT was also expressed in all 46 PPTs studied. The proportions of HIOMT-immunoreactive cells successively decreased in the following tumors: pineocytoma, pineal parenchymal tumor of intermediate differentiation, and pineoblastoma. A few HIOMT-immunoreactive cells were observed in one of 6 primitive neuroectodermal tumors and 23 of 42 medulloblastomas. These results indicate that HIOMT immunohistochemistry may be useful for the diagnosis of PPTs and be a prognostic factor in PPTs.
 ...
PMID:Expression of hydroxyindole-O-methyltransferase enzyme in the human central nervous system and in pineal parenchymal cell tumors. 2041 77


<< Previous 1 2