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)

To examine the sequence complexity and differential expression of human alpha-tubulin genes, we constructed cDNA libraries from two unrelated tissue types (epidermis and fetal brain). The complete sequence of a positively hybridizing alpha-tubulin clone from each library is described. Each is shown to represent an abundantly expressed gene from fetal brain and keratinocytes, respectively. Although the coding regions are extensively homologous (97%), the 3' untranslated regions are totally dissimilar. This property has been used to dissect the human alpha-tubulin multigene family into members bearing sequence relatedness in this region. Surprisingly, each of these noncoding regions shares very high (65 to 80%) interspecies homology with the 3' untranslated region of one of the two rat alpha-tubulin genes of known sequence. These unexpected homologies imply the existence of selective pressure on the 3' untranslated regions of some cytoskeletal genes which maintains sequence fidelity during the course of evolution, perhaps as a consequence of an as yet unidentified functional requirement.
Mol Cell Biol 1983 Oct
PMID:Expression of human alpha-tubulin genes: interspecies conservation of 3' untranslated regions. 664 20

The interphase cell of Crithidia fasciculata has three discrete tubulin populations: the subpellicular microtubules, the axonemal microtubules, and the nonpolymerized cytoplasmic pool protein. These three tubulin populations were independently and selectively purified, yielding, in each case, microtubule protein capable of self-assembly. All three preparations polymerized to form ribbons and sheets rather than the more usual microtubular structures. Analyses of the tubulin by two-dimensional polyacrylamide gel electrophoresis, isoelectric focusing, and peptide mapping indicated that the beta-tubulin complex remained constant regardless of source but that some heterogeneity was present in the alpha subunit. Cytoplasmic pool alpha tubulins (alpha 1/alpha 2) were the only alpha isotypes in the cytoplasm and also formed most of the alpha tubulin species in the pellicular fraction. Flagellar alpha tubulin (alpha 3) was the sole alpha isotype in the flagella; it appeared in small amounts in the pellicular fraction but was completely absent from the cytoplasm. In vitro translation products from polyadenylated RNA from C. fasciculata were also examined by two-dimensional polyacrylamide gel electrophoresis and possessed a protein corresponding to alpha 1/alpha 2 tubulin but lacked any alpha 3 tubulin. The alpha 3 polypeptide arose from a post-translational modification of a precursor polypeptide not identifiable by two-dimensional polyacrylamide gel electrophoresis as alpha 3. Peptide mapping data indicated that cytoplasmic alpha tubulin is the most likely precursor. These results demonstrate alpha-tubulin heterogeneity in this organism and also how close the relationship between flagellar and cytoskeletal tubulins can be among lower eucaryotes.
Mol Cell Biol 1984 Apr
PMID:Tubulin heterogeneity in the trypanosome Crithidia fasciculata. 671 41

A dramatic change in the pattern of protein synthesis occurs within ten minutes after fertilization of Spisula oocytes. This change is regulated entirely at the translational level. We have used DNA clones complementary to five translationally regulated messenger RNAs to follow shifts in mRNA utilization at fertilization and to characterize alterations in mRNA structure that accompany switches in translational activity in vivo. Four of the mRNAs studied are translationally inactive in the oocyte. After fertilization two of these mRNAs are completely recruited onto polysomes, and two are partially recruited. All four of these mRNAs have very short poly(A) tracts in the oocyte; after fertilization the poly(A) tails lengthen considerably. In contrast, a fifth mRNA, that encoding alpha-tubulin mRNA, is translated very efficiently in the oocyte and is rapidly lost from polysomes after fertilization. Essentially all alpha-tubulin mRNA in the oocyte is poly(A)+ and a large portion of this mRNA undergoes complete deadenylation after fertilization. These results reveal a striking relationship between changes in adenylation and translational activity in vivo. This correlation is not perfect, however. Evidence for and against a direct role for polyadenylation in regulating these translational changes is discussed. Changes in poly(A) tails are the only alterations in mRNA sizes that we have been able to detect. This indicates that, at least for the mRNAs studied here, translational activation is not due to extensive processing of larger translationally incompetent precursors. We have also isolated several complementary DNA clones to RNAs encoded by the mitochondrial genome. Surprisingly, the poly(A) tracts of at least two of the mitochondrial RNAs also lengthen in response to fertilization.
J Mol Biol 1983 May 25
PMID:Sequence-specific adenylations and deadenylations accompany changes in the translation of maternal messenger RNA after fertilization of Spisula oocytes. 685 49

The arrangement of developmentally regulated alpha- and beta-tubulin genes has been studied in the parasitic protozoan Leishmania enriettii by using Southern blot hybridization analysis. The alpha-tubulin genes occur in a tandem repeat whose monomeric unit may be represented by a 2-kilobase PstI fragment. Similarly, the beta-tubulin genes probably occur in a separate tandem repeat consisting of approximately 4-kilobase units unlinked to the alpha-tubulin repeats.
Mol Cell Biol 1983 Jun
PMID:Tandem arrangement of tubulin genes in the protozoan parasite Leishmania enriettii. 687 38

The time course of mRNA expressions of two cytoskeletal proteins, beta-actin and alpha-tubulin, was studied by Northern blot analysis and in situ hybridization in the same gerbil brains at various periods of recirculation following 10 min of forebrain ischemia. On Northern blot analysis, beta-actin mRNA in the forebrain showed increase after 6 h and 24 h recirculation. There was wide variation in its expression 3 days postischemia (PI), and by 7 days PI it had returned to control. The alpha-tubulin mRNA in the forebrain was shown to be reduced 6 h PI in our previous study. In the present analysis of Northern blots of delayed postischemic periods, there was no significant change in its expression even though there were variations. In situ hybridization revealed a decline in the mRNA expressions of both alpha-tubulin and beta-actin in the CA1 region as early as 6-24 h PI with the reductions being prominent at 3 days PI. By 7 days PI, beta-actin was only faintly visible while alpha-tubulin was completely absent in the CA1 region. Neither RNA was detectable in CA1 1 month PI. The heat shock-70 protein was expressed by 1 h PI, and it continued to be expressed up to 24 h, returning to control by 3 days PI. These results indicate that ischemia inhibits mRNA expressions of cytoskeletal protein in the selectively vulnerable region of the brain, i.e. CA1. The time course of the reduction of the two mRNAs coincides with delayed neuronal death suggesting that the cytoskeletal proteins may play important roles in selective postischemic neuronal injury.
Brain Res Mol Brain Res 1995 May
PMID:Expression of beta-actin and alpha-tubulin mRNA in gerbil brain following transient ischemia and reperfusion up to 1 month. 760 36

Mammalian cells regulate tubulin mRNA abundance by a posttranscriptional mechanism dependent on the concentration of tubulin monomer. Treatment of mammalian cells with microtubule-depolymerizing drugs and microtubule-polymerizing drugs causes decreases and increases in tubulin mRNA, respectively (D. W. Cleveland, Curr. Opin. Cell Biol. 1:10-14, 1989). In striking contrast to the case with mammalian cells, perturbation of microtubules in Tetrahymena thermophila by microtubule-depolymerizing or -polymerizing drugs increases the level of the single alpha-tubulin gene message by increasing transcription (L. A. Stargell, D. P. Heruth, J. Gaertig, and M. A. Gorovsky, Mol. Cell. Biol. 12:1443-1450, 1992). In this report we show that antimicrotubule drugs preferentially induce the expression of one of two beta-tubulin genes (BTU1) in T. thermophila. In contrast, deciliation induces expression of both beta-tubulin genes. Tubulin gene expression was examined in a mutant strain created by transformation with an in vitro-mutagenized beta-tubulin gene that conferred resistance to microtubule-depolymerizing drugs and sensitivity to the polymerizing drug taxol and in a strain containing a nitrosoguanidine-induced mutation in the single alpha-tubulin gene that conferred the same pattern of drug sensitivities. In both cases the levels of tubulin mRNA expression from the drug-inducible BTU1 gene in the mutant cells paralleled the altered growth sensitivities to microtubule drugs. These studies demonstrate that T. thermophila has distinct, gene-specific mechanisms for modulating tubulin gene expression depending on whether ciliary or cytoplasmic microtubules are involved. They also show that the cytoplasmic microtubule cytoskeleton itself participates in a signal transduction pathway that regulates specific tubulin gene transcription in T. thermophila.
Mol Cell Biol 1995 Sep
PMID:Gene-specific signal transduction between microtubules and tubulin genes in Tetrahymena thermophila. 765 34

The polymerization of alpha- and beta-tubulin into microtubules results in a complex network of microfibrils that have important structural and functional roles in all eukaryotic cells. In addition, microtubules can interact with a diverse family of polypeptides which are believed to directly promote the assembly of microtubules and to modulate their functional activity. We have demonstrated that the c-Myc oncoprotein interacts in vivo and in vitro with alpha-tubulin and with polymerized microtubules and have defined the binding site to the N-terminal region within the transactivation domain of c-Myc. In addition, we have shown that c-Myc colocalizes with microtubules and remains tightly bound to the microtubule network after detergent extraction of intact cells. These findings suggest a potential role for Myc-tubulin interaction in vivo.
Mol Cell Biol 1995 Sep
PMID:The N-terminal domain of c-Myc associates with alpha-tubulin and microtubules in vivo and in vitro. 765 36

The intensity of p75NGFR receptor-like immunoreactivity and the mRNAs encoding p75NGFR, T alpha 1 alpha-tubulin, GAP-43 and the myelin proteins MBP and PLP were measured in the developing cerebellum to study the effects of perinatal thyroid hormone imbalance in rats. Results compared to age-matched controls provide in vivo evidence for differential gene regulation by thyroid hormone in the developing cerebellum. We found that p75NGFR immunoreactivity was strikingly elevated in hypothyroid rats, whereas p75NGFR mRNA content remained only twice as high as that of control levels on postnatal day 15 (P15). When p75NGFR immunoreactivity was still elevated in hypothyroid rats, Purkinje cells exhibited proximal axonal varicosities, axonal twisting and differences in axonal caliber. The mRNAs encoding proteins involved with neurite growth-promoting elements, T alpha 1 alpha-tubulin and GAP-43, were also increased in hypothyroidism, possibly reflecting a neuronal response to a deficiency in, or damage to, cerebellar neurons, or a general delay in their down regulation. Similar increases were not observed for the myelin specific genes. MBP and PLP mRNAs were first detected on P2 of hyperthyroid rats, and they increased with age. Hypo- or hyperthyroidism did not affect the initial onset of MBP and PLP expression, however, hyperthyroidism increased levels of PLP and MBP mRNAs between P2 and P10. By contrast, the most consistent decrease in MBP and PLP mRNAs in rats with thyroid hormone deficiency was observed only on P10. At later times (P15 and P30), the two mRNA levels were similar to controls in all groups. These results are consistent with a role for thyroid hormone in the earlier stages of cerebellar myelination. Hypothryoidism led to specific increases in T alpha 1 alpha-tubulin and GAP-43 mRNAs, and in the immunoreactivity and mRNA levels of p75NGFR receptor--all changes that may play a role in the observed abnormal neuronal outgrowth.
Brain Res Mol Brain Res 1993 Mar
PMID:Gene expression in the developing cerebellum during perinatal hypo- and hyperthyroidism. 768 63

Neuronal differentiation is accompanied by extensive reorganization of the cytoskeleton to initiate the extension of neuritic processes. We have used the rat PC12 pheochromocytoma cell line to examine the role of protein tyrosine kinase activity in the induction of these events. Immunoblotting with phosphotyrosine antibodies revealed that tyrosine phosphorylation of alpha-tubulin in PC12 cells occurred within 10 min of nerve growth factor (NGF) treatment. Tyrosine phosphorylation of alpha-tubulin also occurred on induction of pp60v-src expression in a PC12 cell line (PC12-B9) harboring an inducible v-src gene under transcriptional control of the mouse metallothionine I gene promoter. Two tyrosine phosphorylated proteins in NGF- and pp60v-src induced PC12 cells were identified as alpha-tubulin isoforms by comigration with alpha-tubulin on two-dimensional gel electrophoresis, and by immunoprecipitation with phosphotyrosine antibodies followed by immunoblotting with a monoclonal antibody specific for alpha-tubulin. These results demonstrate that alpha-tubulin is an in vivo tyrosine kinase substrate, which is phosphorylated as an early event in the neuronal differentiation pathway of PC12 cells in response to NGF or pp60v-src. Tyrosine phosphorylation of alpha-tubulin could conceivably alter microtubule dynamics during induction of neurite extension.
J Mol Neurosci 1993
PMID:Tyrosine phosphorylation of alpha-tubulin is an early response to NGF and pp60v-src in PC12 cells. 769 12

We have studied the effects of vinblastine sulfate (VBL) and colchicine (COL) on male rat in vivo and in vitro meiosis. A novel methodology based on isolating a segment of seminiferous tubules containing meiotically dividing spermatocytes was applied. During meiotic divisions at stage XIV of rat spermatogenesis, both chemicals induced only low frequencies of micronuclei (MN), 0.8-3.2 MN/1,000 spermatids. Fluorescence in situ hybridization experiments in mice with the mouse centromere-specific gamma-satellite DNA probe showed that 50.7% of VBL-induced MN and 56.6% of COL-induced MN were centromere positive, indicating that the MN induced by both chemicals contained detached chromosomes. The inhibition of cell proliferation was determined by counting the number of cells arrested at metaphase during the first meiotic (MI) or the second meiotic (MII) division. VBL was found to be a potent inducer of cell death while COL was not. The direct effects of VBL and COL on the meiotic spindles were evaluated using immunohistochemistry with anti-alpha-tubulin and confocal microscopy. In the control animals a significant difference was observed between the mean length of metaphase spindles of MI and MII. Both were dramatically decreased 6 hr after treatment with 2.0 mg/kg of VBL and 0.8 mg/kg of COL, respectively. At 18 hr after COL injection the spindles had about the same length as in the controls. However, the VBL-induced shortening was even more evident at 18 hr for both MI and MII. The possible reasons for observed differences between the two chemicals and between meiosis and mitosis are discussed.
Environ Mol Mutagen 1995
PMID:Effects of vinblastine and colchicine on male rat meiosis in vivo: disturbances in spindle dynamics causing micronuclei and metaphase arrest. 769 4


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