Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

beta-Tubulin synthesis in eucaryotic cells is subject to control by an autoregulatory posttranscriptional mechanism in which the first four amino acids of the beta-tubulin polypeptide act either directly or indirectly to control the stability of beta-tubulin mRNA. To investigate the contribution of this amino-terminal domain to microtubule assembly and dynamics, we introduced a series of deletions encompassing amino acids 2 to 5 of a single mammalian beta-tubulin isotype, M beta 1. Constructs carrying such deletions were inserted into an expression vector, and the ability of the altered polypeptide to coassemble into microtubules was tested by using an anti-M beta 1-specific antibody. We show that the M beta 1 beta-tubulin polypeptide was competent for coassembly into microtubules in transient transfection experiments and in stably transfected cell lines when it lacked either amino acid 2 or amino acids 2 and 3. The capacity of these mutant beta-tubulins to coassemble into polymerized microtubules was only slightly diminished relative to that of unaltered beta-tubulin, and their expression did not influence the viability or growth properties of cell lines carrying these deletions. However, more extensive amino-terminal deletions either severely compromised or abolished the capacity for coassembly. In analogous experiments in which alterations were introduced into the amino-terminal domain of a mammalian alpha-tubulin isotype, M alpha 4, deletion of amino acid 2 did not affect the ability of the altered polypeptide to coassemble, although removal of additional amino-terminal residues essentially abolished the capacity for competent coassembly. The stability of the altered assembly-competent alpha- and beta-tubulin polypeptides was measured in pulse-chase experiments and found to be indistinguishable from the stability of the corresponding unaltered polypeptides. An assembly-competent M alpha 4 polypeptide carrying a deletion encompassing the 12 carboxy-terminal amino acids also had a half-life indistinguishable from that of the wild-type alpha-tubulin molecule. These data suggest that the universally conserved amino terminus of beta-tubulin acts largely in a regulatory role and that the carboxy-terminal domain of alpha-tubulin is not essential for coassembly in mammalian cells in vivo.
Mol Cell Biol 1989 Aug
PMID:Assembly properties of altered beta-tubulin polypeptides containing disrupted autoregulatory domains. 267 73

Rhizoxin and ansamitocin P-3 (a maytansinoid compound), potent inhibitors of mammalian brain tubulin assembly, inhibit growth of a variety of fungi including Aspergillus nidulans. Mutants of A. nidulans, benA10 which is a benomyl resistant beta-tubulin gene mutant and tubA1 which is a benomyl supersensitive alpha-tubulin gene mutant, were both sensitive to rhizoxin and ansamitocin P-3 to the same extent as wild-type strains. We isolated 18 rhizoxin resistant mutants of A. nidulans. All of these mutants were cross-resistant to ansamitocin P-3, but not to benzimidazole antimitotic drugs. These mutants mapped to two loci, rhiA and rhiB, and all of those with high resistance mapped to rhiA. The fact that the protein extracts of rhiA mutants lost rhizoxin binding affinity and that rhiA was closely linked to benA, the major beta-tubulin gene in A. nidulans, indicated that rhiA must be a structural gene for beta-tubulin and that rhiA mutants are a new class of beta-tubulin gene mutants. All of this suggested that, in A. nidulans, these antimitotic drugs bind to beta-tubulin, and that rhizoxin and ansamitocin P-3 share the same binding site but the site does not overlap with the benzimidazole binding site. Protein extracts from a rhiB mutant retained rhizoxin binding affinity, therefore this rhizoxin resistance mechanism should not be a tubulin mediated process.
Mol Gen Genet 1989 Dec
PMID:Rhizoxin resistant mutants with an altered beta-tubulin gene in Aspergillus nidulans. 269 73

As a step towards identifying exploitable differences between host and parasite at the molecular level, we have isolated and sequenced genomic clones encompassing an entire alpha-tubulin gene (designated alpha-tubulin I) from the human malaria parasite, Plasmodium falciparum. The gene, which contains two introns, encodes a product with a predicted length of 453 amino acid residues (50.3 kD). The protein sequence shows a high degree of homology to other alpha-tubulins, particularly that of the coccidian parasite, Toxoplasma gondii (94%), whose gene carries introns in identical positions. Only one copy of the alpha-tubulin I gene itself was found, although a second gene designated alpha-II was also identified which is closely related but which differs at both the nucleotide and amino acid sequence levels. The alpha-I and beta-tubulin genes were found to reside on different chromosomes.
Mol Microbiol 1989 Nov
PMID:Isolation of alpha-tubulin genes from the human malaria parasite, Plasmodium falciparum: sequence analysis of alpha-tubulin. 269 1

Detachment of flagella in Chlamydomonas reinhardii stimulates a rapid accumulation of tubulin mRNAs. The induced tubulin mRNAs are normally rapidly degraded following flagellar regeneration, but inhibition of protein synthesis with cycloheximide prevents their degradation. alpha-Tubulin poly(A) tail lengths were measured during normal accumulation and degradation, and in cycloheximide-treated cells. To measure alpha-tubulin mRNA poly(A) chain lengths with high resolution, specific 3' fragments of alpha 1- and alpha 2-tubulin mRNAs, generated by RNase H digestion of mRNA-oligonucleotide hybrids, were sized by Northern analysis. Both alpha-tubulin mRNAs have a newly synthesized poly(A) chain of about 110 adenylate residues. The poly(A) tails shorten with time, and show an average length of 40 to 60 adenylate residues by 90 minutes after deflagellation, at which time induced alpha-tubulin mRNA is being rapidly degraded. Poly(A) loss is significantly accelerated in cycloheximide-treated cells, and this loss is not attributible simply to the longer time the stabilized molecules spend in the cytoplasm. A large fraction of alpha-tubulin mRNA accumulates as mRNA with very short poly(A) tails (less than 10 residues) in the presence of cycloheximide, indicating that deadenylated alpha-tubulin mRNAs can be stable in vivo, at least in the absence of protein synthesis. The rate and extent of poly(A) loss in cycloheximide are greater for alpha 2-tubulin mRNA than for alpha 1-tubulin mRNA. This difference cannot be attributed to differential ribosome loading. This finding is interesting in that the two mRNAs are very similar in sequence with the exception of their 3' untranslated regions.
J Mol Biol 1989 Jun 20
PMID:Accelerated poly(A) loss on alpha-tubulin mRNAs during protein synthesis inhibition in Chlamydomonas. 276 Sep 30

We have examined changes in the relative synthesis of individual proteins in promastigotes of Leishmania major subjected to decreasing serum levels in vitro. We observed increases in the relative synthesis of the putative heat-shock proteins of 82 and 70 kDa and of proteins of 79 and 41 kDa but decreases in the synthesis of proteins of 38 and 28 kDa. The relative synthesis of alpha-tubulin increased, whereas that of beta-tubulin decreased, in promastigotes subjected to decreased serum concentrations. This uncoordinated regulation of the synthesis of the tubulin proteins was not reflected as an alteration in the relative levels of the messenger RNA of the respective proteins. We have also studied changes in the synthesis of proteins in L. major promastigotes subjected to a temperature change from 26 degrees C to 34 degrees C. The results indicate that the synthesis of putative heat-shock proteins of 82, 70, 65, 41, 23 and 22 kDa increased when the parasites were incubated at the higher temperature, although these proteins were synthesised in detectable amounts at 26 degrees C. We could not detect differences between infective and non-infective promastigotes, separated by binding to peanut agglutinin, in the synthesis of individual proteins in response to increased temperature. These results were confirmed by densitometer analysis of autoradiographs of labelled promastigote proteins, and the relative changes in the synthesis of the two major heat-shock proteins, as well as alpha- and beta-tubulin, were estimated.
Mol Biochem Parasitol 1989 Jun 01
PMID:The influence of temperature and serum deprivation on the synthesis of heat-shock proteins and alpha and beta tubulin in promastigotes of Leishmania major. 276 70

Chicken erythroid cells at different stages of maturation were incubated with [14C]tyrosine to analyze the incorporation of this amino acid into the COOH-terminus of alpha-tubulin. The incorporated radioactivity was determined in the microtubule and nonassembled tubulin pools. At all maturation stages, nonassembled tubulin was more labeled than microtubules. Microtubules were significantly labeled in proerythroblasts, labeled to a lesser extent in erythroblasts and not labeled at all in mature erythrocytes. We also studied the distribution of the tyrosinating and detyrosinating enzymes, tubulin:tyrosine ligase and tubulin carboxypeptidase, respectively, between the assembled and nonassembled tubulin fractions. Tubulin:tyrosine ligase behaved as a soluble entity at all maturation stages, whereas tubulin carboxypeptidase was found partially associated with microtubules in chicken proerythroblasts and completely soluble in mature erythrocytes. The marginal band of toad erythrocytes was examined by immunofluorescence using antibodies specific to tyrosinated and to detyrosinated tubulin. This marginal band which is mainly tyrosinated could be detyrosinated by exposure of these cells, previously permeabilized, to exogenously supplied tubulin carboxypeptidase. Toad erythrocytes contained soluble tubulin carboxypeptidase which showed an activity similar to that of chicken erythrocytes.
Mol Cell Biochem 1989 Aug 15
PMID:Tyrosination-detyrosination of tubulin and microtubules during the development of chick erythrocytes. 277 46

We have cloned alpha- and beta-tubulin cDNAs from Giardia lamblia and have used these to determine the gene copy number in the organism and to isolate alpha- and beta-tubulin genomic clones. Studies of the gene organization demonstrate that two copies of beta-tubulin are linked in a head-to-head configuration. The DNA from these two copies and that from one alpha-tubulin copy has been sequenced upstream of the translation initiation codon, and analyzed for consensus to typical eukaryotic promoter sequences. Characterization of the alpha- and beta-tubulin mRNAs in this parasite by primer extension and S1 nuclease mapping has revealed an unusually short (6 nucleotides) 5' untranslated region.
Mol Biochem Parasitol 1989 Aug
PMID:Evidence for unusually short tubulin mRNA leaders and characterization of tubulin genes in Giardia lamblia. 281 42

A subcloned portion of the 5' nontranslated sequence from a Physarum alpha-tubulin cDNA is specific for a single alpha-tubulin locus, altB, of Physarum polycephalum. We find that this locus is expressed only in the plasmodium and encodes at least an alpha 1-tubulin isotype, which we have designated alpha 1B. Hybridization patterns of other subclones of this cDNA reveal two sequences for alpha-tubulin at the altB locus.
Mol Cell Biol 1987 Sep
PMID:Developmental regulation and identification of an isotype encoded by altB, an alpha-tubulin locus in Physarum polycephalum. 282 27

The expression of an alpha-tubulin gene (altB1 (N alpha Tu) [(1987) J. Mol. Biol. 193, 427-438]) of Physarum polycephalum (strain CLdAXE) was found to be governed by a developmental switch since mRNA transcripts were detected, by S1 nuclease analysis, in the plasmodial but not the amoebal phase of the life-cycle. The conclusion that the altB1 (N alpha Tu) allele codes for a plasmodial specific alpha-tubulin isotype is supported by recent amino acid sequence data.
 ...
PMID:Differential expression of an alpha-tubulin gene during the development of Physarum polycephalum. 288 21

We have investigated the regulation of glutamine synthetase (GS) mRNA synthesis in Chinese hamster ovary cell mutants which overproduce GS and contain an amplified GS gene. Specific mRNA synthesis was analyzed by measuring elongation of transcripts in isolated nuclei. Transcription was assayed by hybridization of newly synthesized [32P]RNA to a genomic GS clone. Nuclear transcript elongation was inhibited more than 90% by alpha-amanitin. The relative rates of GS mRNA synthesis in nuclei from cells incubated for 2 days with no additions, insulin, dexamethasone, or (Bu)2cAMP are 186, 419, 375, and 227 ppm, respectively. The insulin- and dexamethasone-mediated increases in GS transcription rate (2-fold) were associated with 3.7- and 5.8-fold increases in GS mRNA abundance. By contrast, alpha-tubulin gene transcription was not altered by insulin or dexamethasone; however, it was decreased by (Bu)2cAMP.
Mol Endocrinol 1987 Jun
PMID:Insulin and dexamethasone stimulate transcription of an amplified glutamine synthetase gene in Chinese hamster ovary cells. 290 59


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>