Disease relevance of TUBBP1

• Cellular extracts derived from pheochromocytoma cells (PC12-) inhibit the assembly of calf brain tubulin, while those derived from nerve growth factor-differentiated cells (PC12+) do not display this effect [1].
• In studies exploring the mechanism(s) of signal transduction for these distinct neutrophil responses, we found that the fMet-Leu-Phe-induced stimulation of tubulin tyrosinolation in PMNs and in differentiated HL-60 cells is completely blocked by pertussis toxin, while the PMA-induced random incorporation of tyrosine is not inhibited [2].
• He argues that microtubule inhibitors are not equally toxic to all proliferating cells but, by virtue of differential tubulin binding, show selective toxicity that might allow their use as antimalarial drugs [3].
• Here, we present one such analog, 9-nitro-noscapine (9-nitro-nos), which binds tubulin and induces apoptosis selectively in tumor cells (ovarian and T-cell lymphoma) resistant to paclitaxel, vinblastine, and teniposide [4].
• Tubulin from neuroblastoma cells has an isotubulin distribution grossly similar to non-neuronal sources but additionally contains two basic beta isotubulins found in adult brain that are absent from non-neuronal tissues [5].

Psychiatry related information on TUBBP1

• Further, it was also observed that REM sleep deprivation decreased amounts of actin and tubulin in neurons confirming our previous reports of changes in neuronal size and shape after such deprivation [6].
• Selectively increased oxidative modifications mapped to detergent-insoluble forms of Abeta and beta-III tubulin in Alzheimer's disease [7].
• Histone deacetylase 6 inhibition compensates for the transport deficit in Huntington's disease by increasing tubulin acetylation [8].

High impact information on TUBBP1

• Targeting efficiency was higher with a linearized than with a circular construct, and with 5 kilobases of tubulin gene cluster than with 0.9 kilobases [9].
• We have obtained long-term stable transformants of T. brucei that have acquired the ability to grow in medium containing the drug G418, following the targeted insertion of the bacterial gene for neomycin phosphotransferase (neo(r) gene) into the trypanosome tubulin cluster [9].
• Evidence that a human beta-tubulin pseudogene is derived from its corresponding mRNA [10].
• The past decade has witnessed the identification and characterization of bacterial homologs of the three major eukaryotic cytoskeletal families: actin, tubulin and intermediate filaments [11].
• Determination of tau protein structure has revealed three 18 amino acid repeated sequences hypothesized to be tubulin binding sites [12].

Chemical compound and disease context of TUBBP1

• These compounds are cytotoxic at nanomolar concentrations in neuroblastoma cells, display a similar structure-activity relationship compared to combretastatin A4, and inhibit tubulin polymerization [13].
• Current therapies for microsporidiosis include benzimidazoles, which bind tubulin-inhibiting microtubule assembly, and fumagillin and its derivatives, which bind and inhibit methionine amino peptidase type 2 (MetAP2) [14].
• Albendazole (ABZ), a benzimidazole carbamate used for the treatment of several human helminthiases has high affinity for tubulin, which results in an inhibition of microtubule polymerization, blocking several vital processes in the parasites, such as motility and nutrient uptake [15].
• In the present study, we report that membrane-impermeable testosterone-bovine serum albumin (BSA) acts synergistically with paclitaxel in modifying actin and tubulin cytoskeleton dynamics in LNCaP (androgen sensitive) and DU-145 (androgen insensitive) human prostate cancer cell lines [16].

Biological context of TUBBP1

• The inhibition of microtubule formation was shown to be mediated by interference with the colchicine binding site of tubulin [17].
• The role of microtubules in platelet aggregation and secretion has been analyzed using platelets permeabilized with digitonin and monoclonal antibodies to alpha (DM1A) and beta (DM1B) subunits of tubulin [18].
• CONCLUSION: Alternating and monotypic tubulin arrays were found to be mutually exclusive through comparison of genome sequences [19].
• Polycistronic transcription in these organisms makes the chromosomal arrangement of tubulin genes important with respect to gene expression [19].
• In TTL-null fibroblasts, tubulin detyrosination and CAP-Gly protein mislocalization correlate with defects in both spindle positioning during mitosis and cell morphology during interphase [20].

Anatomical context of TUBBP1

• [4-(Imidazol-1-yl)thiazol-2-yl]phenylamines. A Novel Class of Highly Potent Colchicine Site Binding Tubulin Inhibitors: Synthesis and Cytotoxic Activity on Selected Human Cancer Cell Lines [17].
• beta-Tubulin Is a More Suitable Internal Control than beta-Actin in Western Blot Analysis of Spinal Cord Tissues after Traumatic Injury [21].
• We aimed thus to study the effects of different tubulin ligands on the changes in the microtubule network and in several markers of cell injury and oxidative activity in cardiac muscle cells submitted to a reversible substrate-free, hypoxia-reoxygenation model of ischemia-reperfusion [22].
• Now, we found that in CAD cells, ATPase is not activated by L-glutamate and tubulin/ATPase complex is not present in membranes [23].
• In cells of neural and non-neural origin, tubulin forms a complex with plasma membrane Na(+),K(+)-ATPase, resulting in inhibition of the enzyme activity [23].

Associations of TUBBP1 with chemical compounds

• Inhibition of actin or tubulin polymerization, by using cytochalasin B or nocodazole, respectively, altered OP morphology and markedly impaired migration [24].
• Tubulin-associated drug targets: Aurora kinases, Polo-like kinases, and others [25].
• Neither compound seemed to induce an aberrant tubulin assembly reaction, as occurs with vinblastine (tight spirals) or dolastatin 10 (aggregated rings and spirals) [26].
• Comparison of the Activities of the Truncated Halichondrin B Analog NSC 707389 (E7389) with Those of the Parent Compound and a Proposed Binding Site on Tubulin [26].
• Cytosolic tubulin from trichostatin A-treated but not from non-treated cells inhibited ATPase activity [23].

Physical interactions of TUBBP1

• Tubulin was identified as one example of a protein that can interact with ankyrin repeats that are not recognized by the anion exchanger [27].

Other interactions of TUBBP1

• The purified insulin receptor kinase catalyzed the phosphorylation of native tubulin and microtubule-associated proteins (MAPs; MAP2, tau) on tyrosine residues [28].
• In this study an immunofluorescence comparison of these minor populations of microtubules revealed that, in African green monkey kidney epithelial cells (TC-7 line), the population of microtubules enriched in detyrosinated tubulin was virtually coincident with the population enriched in acetylated alpha tubulin [29].
• Studies of signal transduction in the respiratory burst-associated stimulation of fMet-Leu-Phe-induced tubulin tyrosinolation and phorbol 12-myristate 13-acetate-induced posttranslational incorporation of tyrosine into multiple proteins in activated neutrophils and HL-60 cells [2].
• A synthetic peptide with sequence EMYEDDEEESESQGPK, corresponding to that of the COOH terminus of beta 3-tubulin, was efficiently phosphorylated in vitro by casein kinase II at the same serine 444 [30].
• These observations suggest that a significant portion of hsp90 is associated with a tubulin-containing complex both in a hypotonic cytosol preparation from mouse fibroblasts and in intact marsupial kidney epithelial cells [31].

Analytical, diagnostic and therapeutic context of TUBBP1

• (1) Coprecipitation of the proteins at low ionic strength at which tubulin by itself did not precipitate and (2) affinity chromatography on columns of immobilized myosin [18].
• We used cryo-electron microscopy and unidirectional surface shadowing to elucidate the structure and conformation of HURP-induced tubulin sheets and their interaction with the inner microtubule [32].
• Tubulin-binding drug screening by MALDI-TOFMS [33].
• Microinjection of fluorescent tubulin into dividing sea urchin cells [34].
• The relative amounts of actin, tubulin, and neurofilament polypeptides in the operated ventral roots were measured by quantitative densitometry of stained two-dimensional electrophoretic gels [35].

References