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

A Saccharomyces cerevisiae homolog to Drosophila melanogaster and mouse Tcp-1 encoding tailless complex polypeptide 1 (TCP1) has been identified, sequenced, and mapped. The mouse t complex has been under scrutiny for six decades because of its effects on embryogenesis and sperm differentiation and function. TCP1 is an essential gene in yeast cells and is located on chromosome 4R, linked to pet14. The TCP1-encoded proteins in yeast, Drosophila, and mouse cells share between 61 and 72% amino acid sequence identities, suggesting a primordial function for the TCP1 gene product. To assess function, we constructed a cold-impaired recessive mutation (tcp1-1) in the yeast gene. Cells carrying the tcp1-1 mutation grew linearly rather than exponentially at the restrictive temperature of 15 degrees C with a generation time of approximately 32 h in minimal medium. Both multinucleate and anucleate cells accumulated with time, suggesting that the linear growth kinetics may be explained by the generation of anucleate buds incapable of further cell division. In addition, the multinucleate and anucleate cells contained morphologically abnormal structures detected by anti-alpha-tubulin antibodies. The kinetics of appearance of these abnormalities suggest that they are a direct consequence of loss of function of the TCP1 protein and not a delayed, indirect consequence of cell death. We also observed that strains carrying tcp1-1 were hypersensitive to antimitotic compounds. Taken together, these observations imply that the TCP1 protein affects microtubule-mediated processes.
Mol Cell Biol 1991 May
PMID:The yeast homolog to mouse Tcp-1 affects microtubule-mediated processes. 190 44

The molecular basis for the resistance of the sheep parasitic nematode Haemonchus contortus to the benzimidazole (BZ) group of anthelmintics was investigated. Three BZ-susceptible and three resistant populations from different geographical locations were characterized with respect to the egg-hatch assay with thiabendazole (TBZ), mebendazole (MBZ) binding tests and restriction fragment length polymorphism (RFLP) after Southern blotting. Cloned H. contortus alpha- and beta-tubulin genes were used as probes to analyze the RFLPs of genomic DNA prepared from mixtures of infectious larvae (L3) or adults. The susceptible populations showed, with both alpha- and beta-tubulin probes, 2 to 6 different fragments, depending on the restriction enzyme used. The three resistant populations showed as many fragments with the alpha-tubulin probe as the susceptible populations, but when probed with beta-tubulin only 1 or 2 fragments were visible, but always less than in the susceptible populations. An in vitro selection experiment was carried out using a susceptible population that was isolated in the laboratory before BZ came on the market. The results showed that after two selections with increasing amounts of TBZ, the population had become resistant, according to the egg-hatch assay values and MBZ binding assay. Using RFPL, the number of beta-tubulin probe reactive DNA fragments was reduced from 5 to 1. Analysis of the DNA of individual male adults of susceptible populations indicated a heterogeneity among the individual worms regarding the number of beta-tubulin probe reactive fragments (1 to 4) and frequency of the specific fragments. Usually, only one specific fragment (9 kb) was found in the resistant individuals. This 9-kb fragment was already present in some individuals in the susceptible population although it was in combination with other fragments. This would imply that genes conferring BZ resistance were present in H. contortus populations before BZ came on the market, and could explain the fast selection for BZ resistance in the field.
Mol Biochem Parasitol 1990 Nov
PMID:Molecular analysis of selection for benzimidazole resistance in the sheep parasite Haemonchus contortus. 198 Dec 49

We report that the concentration of phosphoenolpyruvate carboxykinase (PEPCK) mRNA increased 5- to 10-fold when H4IIEC3 rat hepatoma cells were cultured at high compared to low density. The magnitude and direction of this response were mRNA specific, as the mRNAs encoding tyrosine aminotransferase and albumin increased approximately 20%, whereas the mRNAs encoding beta-actin and alpha-tubulin decreased 40% and 20%, respectively. Paracrine or autocrine mechanisms were not responsible for the density effect, since conditioned medium or frequent medium changes had only a modest effect on the abundance of PEPCK mRNA. Culture of H4IIEC3 cells at low density or on collagen promoted a flattened morphology and low PEPCK mRNA levels. At high density, cells assumed a cuboidal shape on both plastic and collagen and expressed high PEPCK mRNA levels. Induction of PEPCK mRNA by high density culture did not involve increased intracellular cAMP, since treatment with 8-(4-chlorophenylthio)-cAMP was synergistic with density. High cell density increased PEPCK run-on transcription approximately 3-fold, while PEPCK mRNA increased more than 6-fold. These observations suggest that high culture density increases PEPCK mRNA by increasing its transcription and possibly stabilizing PEPCK mRNA. The response could be coupled to the regulation of cell shape, as a close relationship between cell shape and gene expression has previously been shown to be important in the development and maintenance of tissues and organs. The PEPCK gene in H4IIEC3 cells could provide a useful model in which to study the poorly understood mechanisms involved in coordinating form and function.
Mol Endocrinol 1991 May
PMID:Culture at high density increases phosphoenolpyruvate carboxykinase messenger RNA in H4IIEC3 hepatoma cells. 207 26

We report the isolation and sequencing of genomic clones encompassing the entire alpha-tubulin II gene from the human malaria parasite Plasmodium falciparum. This gene is closely related to, but significant different from the alpha-tubulin I gene that we have described previously. These two genes represent the entire complement of alpha-tubulin sequences in this organism and are expressed in a stage-specific manner. The alpha-II gene is present as a single copy and encodes a tubulin molecule with a predicted length of 450 amino acid residues (49.7 kDa). Like the alpha-I gene, it contains two introns, which are in identical positions to those of alpha-I, but are about one-third smaller. The deduced alpha-II protein is very similar to alpha-tubulin I (94.2% amino acid identity), except for notable differences across residues 40-45. In addition, unlike the great majority of alpha-tubulin genes (including alpha-I), alpha-II does not encode a terminal tyrosine residue. Using pulsed field gel electrophoresis we demonstrate that the two alpha-tubulin genes, together with the single beta-tubulin gene, are unlinked, all residing on different chromosomes. We assign alpha-I to chromosome 9, alpha-II to chromosome 4 and beta-tubulin to chromosome 10.
Mol Biochem Parasitol 1990 Dec
PMID:The tubulin genes of the human malaria parasite Plasmodium falciparum, their chromosomal location and sequence analysis of the alpha-tubulin II gene. 209 Sep 47

Most ciliates use a particular genetic code where the standard stop codons UAA and UAG encode glutamine. Ciliate genes cannot therefore be expressed in heterologous systems such as Escherichia coli. To overcome this problem, we worked out a system of inducible suppression to permit efficient readthrough of UAAs and UAGs: a strong UAA tRNA suppressor that inserts glutamic acid was cloned downstream from a tac promoter whose efficiency was reduced by a transcription terminator. This system proved to be operational (1) to suppress UAG mutations by wobble pairing in an E. coli lacI-lacZ gene fusion and (2) to read through at least eight UAA glutamine codons in a Paramecium alpha-tubulin gene, as detected by Western blotting and colony hybridization. This work opens the way for cloning Ciliate genes from expression libraries and for expressing particular sequences without extended in vitro mutagenesis. A similar approach can be envisaged for expression of genes from Mycoplasma, mitochondria or other genomes that use non-standard genetic codes.
J Mol Biol 1990 Nov 20
PMID:Expression of a ciliate gene in Escherichia coli using a suppressor tRNA to read the UAA and UAG glutamine codons. 212 36

The distributions of the non-tyrosinated M alpha 4 alpha-tubulin gene product and its tyrosinated form M alpha 4 + Y were examined in immunoblots and sections of adult rat brain. In cerebellar sections, M alpha 4 and M alpha 4 + Y immunoreactivities were enriched in neurons, anti-M alpha 4 + Y labeling thus being more restricted in distribution than that of the general alpha-tubulin antibody YL1/2. The results indicate that the M alpha 4 gene product does not constitute the large non-tyrosinatable pool of alpha-tubulin in brain.
Brain Res Mol Brain Res 1990 Jun
PMID:The non-tyrosinated M alpha 4 alpha-tubulin gene product is post-translationally tyrosinated in adult rat cerebellum. 216 3

An oligonucleotide probe (315) specific for the alpha- and beta-tubulin genes of Plasmodium falciparum was synthesized utilizing codon usage of P. falciparum determined from published gene sequences. By screening genomic and cDNA libraries with the oligonucleotide probe, alpha- and beta-tubulin clones were isolated. Positive clones were identified by partial sequencing and comparing the deduced amino acid sequence with the chicken brain alpha- and beta-tubulin amino acid sequences. The beta-tubulin gene was completely sequenced at the genomic level and partially at cDNA level. The deduced polypeptide is 445 amino acids long, shares 88% homology with chicken brain beta-tubulin, and contains two introns of 362 and 163 bp long, respectively. alpha- and beta-tubulin genes of P. falciparum are unlinked and dispersed; more than one copy of each gene may be present. Northern blot analysis of total RNA of the blood-stage parasite indicates the presence of three transcripts of alpha-tubulin (3.3 kb, 2.6 kb, 1.9 kb) and three transcripts of beta-tubulin gene (3.6 kb, 2.9 kb, 2.0 kb). The significance of these transcripts is presently unknown.
Mol Biochem Parasitol 1990 Mar
PMID:Isolation of alpha- and beta-tubulin genes of Plasmodium falciparum using a single oligonucleotide probe. 218 6

Microtubule organization in the cytoplasm is in part a function of the number and length of the assembled polymers. The intracellular concentration of tubulin could specify those parameters. Saccharomyces cerevisiae strains constructed with moderately decreased or increased copy numbers of tubulin genes provide an opportunity to study the cellular response to a steady-state change in tubulin concentration. We found no evidence of a mechanism for adjusting tubulin concentrations upward from a deficit, nor did we find a need for such a mechanism: cells with no more than 50% of the wild-type tubulin level were normal with respect to a series of microtubule-dependent properties. Strains with increased copies of both alpha- and beta-tubulin genes, or of alpha-tubulin genes alone, apparently did down regulate their tubulin levels. As a result, they contained greater than normal concentrations of tubulin but much less than predicted from the increase in gene number. Some of this down regulation occurred at the level of protein. These strains were also phenotypically normal. Cells could contain excess alpha-tubulin protein without detectable consequences, but perturbations resulting in excess beta-tubulin genes may have affected microtubule-dependent functions. All of the observed regulation of levels of tubulin can be explained as a response to toxicity associated with excess tubulin proteins, especially if beta-tubulin is much more toxic than alpha-tubulin.
Mol Cell Biol 1990 Oct
PMID:Regulation of tubulin levels and microtubule assembly in Saccharomyces cerevisiae: consequences of altered tubulin gene copy number. 220 11

Overexpression of alpha- and beta-tubulin genes in Saccharomyces cerevisiae, separately or together, leads to accumulation of large excesses of each of the polypeptides and arrest of cell division. However, other consequences of overexpression of these genes differ in several ways. As shown previously (D. Burke, P. Gasdaska, and L. Hartwell, Mol. Cell. Biol. 9:1049-1059, 1989), overexpression of beta-tubulin leads, at early times, to loss of microtubule structures and loss of viability. Eventually, the excess beta-tubulin forms abnormal structures. We show here that, in contrast, overexpression of alpha-tubulin led to none of these phenotypes and in fact could suppress each of the phenotypes associated with beta-tubulin accumulation. Truncated forms of beta-tubulin that were not competent to carry out microtubule functions also failed to elicit the beta-tubulin-specific phenotypes when overexpressed. The data support the hypothesis that beta-tubulin in excess over alpha-tubulin is uniquely toxic, perhaps because it interferes with normal microtubule assembly.
Mol Cell Biol 1990 Oct
PMID:Phenotypic consequences of tubulin overproduction in Saccharomyces cerevisiae: differences between alpha-tubulin and beta-tubulin. 220 12

We examined the modulation in expression of genes encoding three cytoskeletal elements (beta-actin, gamma-actin, and alpha-tubulin) in Syrian hamster embryo (SHE) cells following exposure to ionizing radiations. Early-passage SHE cells were irradiated in plateau phase with various low doses (12-200 cGy) of neutrons, gamma-rays, or x-rays. RNA samples were prepared from cells at different times postexposure and were analyzed for levels of specific transcripts by northern blots. The results revealed that alpha-tubulin was induced by both high-linear energy of transfer (LET) (neutrons) and low-LET (gamma-rays and x-rays) radiations with similar kinetics. The peak in alpha-tubulin mRNA accumulation occurred between 1 and 3 h postexposure; for gamma-actin mRNA, accumulation was similarly induced. For both gamma-actin and alpha-tubulin, the higher the dose during the first hour postexposure (up to 200 cGy gamma-rays), the greater the level of mRNA induction. In contrast, mRNA specific for beta-actin showed decreased accumulation during the first hour following radiation exposure, and remained low up to 3 h postexposure. These results document the differential modulation of genes specific for cytoskeletal elements following radiation exposure. In addition, they demonstrate a decrease in the ratio of beta-actin:gamma-actin mRNA within the first 3 h following gamma-ray exposure. These changes in mRNA accumulation are similar to those reported in some transformed cell lines and in cells treated with tumor promoters, which suggests a role for changes in actin- and tubulin-mRNA expression in radiation-mediated transformation.
Mol Carcinog 1990
PMID:Effects of ionizing radiation on expression of genes encoding cytoskeletal elements: kinetics and dose effects. 227 32


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