Disease relevance of Tuba1a

• Changes in the expression of the genes encoding alpha-tubulin and a 94,000-dalton protein (p94) specified by a cDNA clone, p4-30, were examined in a differentiated teratocarcinoma-derived parietal endoderm cell line, PYS-2, and an undifferentiated teratocarcinoma stem cell line, F9 [1].
• Neuronal expression of the transcription factor Gli1 using the Talpha1 alpha-tubulin promoter is neuroprotective in an experimental model of Parkinson's disease [2].
• Multipotential embryonal carcinoma cells express mainly one alpha-tubulin isoform (alpha 1) and three beta-tubulin isoforms: a major one (beta 3) and two minor ones (beta 4 and beta 5) [3].
• Previously, we reported that following a chronic nerve resection, removal of the neuroma reversed the atrophy, increased the number of countable motoneurons and resulted in the re-expression of GAP-43 and alpha tubulin mRNA [4].
• Neonatal hypothyroidism - a biochemical disorder of alpha-tubulin metabolism [5].

High impact information on Tuba1a

• Using cloned cDNA probes for beta actin and alpha tubulin, we show that changes in mRNA activity correspond to a specific loss of these sequences during cellular differentiation [6].
• In vitro, purified HDAC6 potently deacetylates alpha-tubulin in assembled microtubules [7].
• Reversible acetylation of alpha-tubulin has been implicated in regulating microtubule stability and function [7].
• Acetylated alpha-tubulin is most abundant in stable microtubules but is absent from dynamic cellular structures such as neuronal growth cones and the leading edges of fibroblasts [7].
• Haploid expression of a mouse testis alpha-tubulin gene [8].

Chemical compound and disease context of Tuba1a

• Testosterone induces neuroprotection from oxidative stress. Effects on catalase activity and 3-nitro-L-tyrosine incorporation into alpha-tubulin in a mouse neuroblastoma cell line [9].

Biological context of Tuba1a

• Five mouse alpha-tubulin isotypes are described, each distinguished by the presence of unique amino acid substitutions within the coding region [10].
• The unexpected prevalence of c-myc and alpha-tubulin in the S-phase library is supported by Northern analysis of RNA from phase-synchronous cells [11].
• In contrast, some populations of astrocytes incorporated nitrotyrosine into alpha-tubulin, but free nitrotyrosine had no effect on the viability and phenotype of astrocytes in culture, as evaluated by glial fibrillary acidic protein immunoreactivity, cell growth and morphology [12].
• Double-labeling studies showed that Talpha1:nlacZ expression was detectable in the same cells and at approximately the same time as was betaIII-tubulin, indicating that detectable transcription of the Talpha1 alpha-tubulin promoter commences at the time of terminal mitosis, at least in culture [13].
• Mock transfections had no effect on HSMC contractily, and transfections with small interfering RNAs (siRNAs) specific for HDAC6, a cytosolic HDAC that functions as an alpha-tubulin deacetylase, resulted in a weak contraction inhibition [14].

Anatomical context of Tuba1a

• Post-transcriptional regulation of the abundance of mRNAs encoding alpha-tubulin and a 94,000-dalton protein in teratocarcinoma-derived stem cells versus differentiated cells [1].
• In elongating spermatids and residual bodies, the synthesis of alpha tubulin is drastically reduced [15].
• Recently, we have shown that Hsp105alpha binds to alpha-tubulin and prevents the heat-induced disaggregation of microtubules [16].
• Our results suggest that a functional relationship may exist between the structure and organization of the Golgi complex and the detyrosination of alpha-tubulin in microtubules [17].
• The relationship between alpha tubulin detyrosination and microtubule (MT) stability was examined directly in cultured fibroblasts by experimentally converting the predominantly tyrosinated MT array to a detyrosinated (Glu) array and then assaying MT stability [18].

Associations of Tuba1a with chemical compounds

• Whereas the 1.8-kb mRNA encodes a distinct alpha-tubulin isotype, the 2.4-kb mRNA is defective in that the methionine residue required for translational initiation is missing [10].
• Clones LG-80, LG-2, and LG-69 are highly homologous to beta-actin, lactate dehydrogenase, and alpha-tubulin [19].
• In the studies reported here, it was found that inhibitors of polyamine biosynthesis, methylglyoxal-bis[quanylhydrazone] (MGBG) and difluoromethylornithine (DFMO), prevent mitogen-induced accumulation of mRNAs encoding major cytoskeletal components, beta-actin and alpha-tubulin, in mouse splenocytes [20].
• Tubulin-tyrosine ligase (TTL), the enzyme responsible for the reversible addition of a tyrosine residue at the carboxyl end of alpha-tubulin, has been purified from porcine brain using a purification scheme based on standard biochemical procedures [21].
• Nocodazole markedly inhibited incorporation of [3H]glutamate into alpha- and beta-tubulin, whereas taxol had no effect for alpha-tubulin and a stimulating effect for beta-tubulin [22].

Regulatory relationships of Tuba1a

• E2F6-deficient mice ubiquitously express the alpha-tubulin 3 and 7 genes, which are expressed strictly testis-specifically in control mice [23].

Other interactions of Tuba1a

• In brain, alpha-tubulin at its basal level was found to be extremely acetylated; and alpha-enolase was shown to be a newly recognized possibly acetylated protein [24].
• Acetylated alpha-tubulin and Cx37 double labelling revealed that the majority of Cx37 gap junctions, irrespective of follicle stage, were located on the outer surface of the oocyte cytoskeleton [25].
• However, relative mRNA expression of IL-2 to a cytoskeletal protein, alpha-Tubulin was lower in 6 to 8-month-old B/W F1 mice than in 2-month-old mice [26].
• To determine whether pRb is required for neuronal determination in vivo, we crossed the Rb-/- mice with transgenic mice expressing beta-galactosidase from the early, panneuronal Talpha1 alpha-tubulin promoter (Talpha1:nlacZ) [27].
• Tubulin is subject to a special cycle of detyrosination/tyrosination in which the C-terminal tyrosine of alpha-tubulin is cyclically removed by a carboxypeptidase and readded by a tubulin-tyrosine-ligase (TTL) [28].

Analytical, diagnostic and therapeutic context of Tuba1a

• Immunoprecipitation experiments show that DVL-1 coimmunprecipitates with spermatogenic cells beta-actin rather than alpha-tubulin [29].
• Northern blot analysis of total mouse mammary RNA that were hybridized with probes to cytoskeletal proteins showed a gradual decrease of alpha-tubulin mRNA, but an increase in beta-actin mRNA during early involution [30].
• Peptide mapping studies demonstrated that the progressive alteration of alpha-tubulin revealed by PAGE analysis cannot be explained by contamination of the alpha-tubulin region by other proteins on gels [31].
• Using rabbit antiserum prepared to a novel synthetic peptide predicted from this mouse testis alpha-tubulin cDNA, we have have detected by immunoblot and indirect immunofluorescence an antigenic epitope present in testicular alpha tubulin that is not detectable in brain alpha tubulins [32].
• Double immunofluorescence studies in exponentially growing or spreading fibroblasts show that SLK is associated with the microtubule network and can be coprecipitated with alpha-tubulin [33].

References