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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have indicated that the concentration of circulating insulin-like growth factor-I (IGF-I) declines in young growing rats that have been fasted or maintained on a protein-deficient diet. To investigate the molecular mechanism(s) by which IGF-I levels are regulated by nutrition, we measured the levels of IGF-I mRNA in 6-week-old male control rats fed ad libitum, rats fasted for 24, 48, or 72 h, and rats fasted for 48 or 72 h and then refed for 24 h. The abundance of several IGF-I mRNA species (8.0, 4.0, 1.7, and 1.0 kilobases) decreased in the fasting animals and rebounded after 24 h of refeeding, although not to the initial control levels. The 1 kilobase IGF-I mRNA species exhibited a 43% decrease after 24 h of fasting, a 76% decrease after 48 h of fasting, and an 82% decrease after 72 h of fasting. Hepatic GH receptor mRNA also decreased in fasting rats. This indicates that the GH receptor down-regulation that occurs in fasting is accompanied by and probably at least partly caused by a decline in GH receptor mRNA. The magnitude and kinetics of the decline in GH receptor mRNA were similar to the magnitude and kinetics of the decline in IGF-I mRNA, suggesting that the two mRNAs may be regulated by a similar mechanism. There was no significant change in the levels of liver beta-actin or serum albumin mRNA under the same conditions, indicating that the regulation of IGF-I and GH receptor mRNA was specific. In addition, the levels of brain IGF-II, beta-actin, and alpha-tubulin mRNAs were not significantly changed by fasting. To further elucidate the molecular mechanism for regulation of hepatic IGF-I mRNA, nuclear transcription elongation assays were performed using nuclei isolated from the liver of control rats, rats fasted for 72 h, and fasted-refed rats. There was considerable animal-to-animal variability in IGF-I gene transcription within each group. The mean level of IGF-I gene transcription was lower in the fasting animals than in the fed controls. However, this decrease was not statistically significant, and the magnitude of the decrease did not account for the 79% decrease in total IGF-I mRNA. These results suggest that IGF-I mRNA is regulated at least partly at the posttranscriptional level.
Mol Endocrinol 1990 Jan
PMID:Effect of fasting on insulin-like growth factor-I (IGF-I) and growth hormone receptor mRNA levels and IGF-I gene transcription in rat liver. 232 71

Tryptic and cyanogen bromide peptides of pig brain alpha- and beta-tubulin reacting with monoclonal antibodies YOL1/34, DM1A and DM1B have been isolated and identified. They all correspond to parts of the C-terminal regions of either alpha- or beta-tubulin, and those peptides reacting with a given antibody have overlapping sequences. In the case of YOL1/34, its relatively high reactivity with small peptides suggests that many of the determinants for this antibody are within the overlapping region of these peptides comprising only nine amino acids in positions alpha 414 to 422. The smallest common region of peptides reacting with the other alpha-tubulin antibody DM1A corresponds to positions alpha 426 to 450, whereby amino acids within the positions 426 and 430 appear to be particularly important for reactivity. Since the last C-terminal residues of alpha-tubulin are also accessible to antibodies and enzymes, it seems that an extensive part (35 to 40 residues) of this very acidic C-terminal domain is exposed on the surface of native tubulin dimers. In microtubules, however, the amino-terminal end of this region appears to be less accessible, as YOL1/34 reacts poorly, if at all, with intact microtubules. All of the peptides reacting with beta-tubulin monoclonal antibody DM1B were derived from the acidic C-terminal domain and they overlapped in positions beta 416 to 430. This indicates that beta-tubulin is also positioned with at least part of its acidic C-terminal domain on the surface of microtubules, since DM1B reacts with unfixed microtubules after microinjection.
J Mol Biol 1986 May 20
PMID:Carboxy-terminal regions on the surface of tubulin and microtubules. Epitope locations of YOL1/34, DM1A and DM1B. 242 29

By using a Trypanosoma brucei alpha-tubulin cDNA probe under reduced stringency hybridization conditions, we have isolated two genomic clones that constitute portions of alpha-tubulin genes of the rodent malarial parasite Plasmodium yoelii. P. yoelii has two alpha-tubulin genes, the 3' portions of which were present in the two clones, Py alpha T1 and Py alpha T2, containing 1.3 kb and 6.6 kb EcoRI fragments respectively. The 1358 bp Py alpha T1 clone was completely sequenced and found to contain 591 nucleotides of uninterrupted coding sequence with a strong bias for AT-rich codons, starting with codon 254 of a consensus alpha-tubulin sequence. Numerous attempts to clone 5' portions of these genes were unsuccessful. A single mRNA of 2.3 kb was recognized by both the clones in the erythrocytic stages of P. yoelii. A probe constituting the untranslated sequences of Py alpha T1 also recognized this RNA but failed to hybridize with Py alpha T2 sequences, indicating that the gene represented by the Py alpha T1 clone was expressed during the erythrocytic stages. The deduced amino acid sequence of the Py alpha T1 gene terminates in Tyr-Glu instead of Glu-Tyr observed in alpha-tubulins of almost all other organisms. The difference observed may have implications for alpha-tubulin metabolism in malarial parasites.
Mol Biochem Parasitol 1988 Aug
PMID:Molecular clones of alpha-tubulin genes of Plasmodium yoelii reveal an unusual feature of the carboxy terminus. 245 18

The process of trans splicing is essential to the maturation of all mRNAs in the Trypanosomatidae, a family of protozoan parasites, and to specific mRNAs in several species of nematode. In Trypanosoma brucei, a 39-nucleotide (nt) leader sequence originating from a small, 139-nt donor RNA (the spliced leader [SL] RNA) is spliced to the 5' end of mRNAs. An intermediate in this trans-splicing process is a Y structure which contains the 3' 100 nt of the SL RNA covalently linked to the pre-mRNA via a 2'-5' phosphodiester bond at the branch point residue. We mapped the branch points in T. brucei alpha- and beta-tubulin pre-mRNAs. The primary branch acceptors for the alpha- and beta-tubulins are 44 and 56 nt upstream of the 3' splice sites, respectively, and are A residues. Minor branch acceptors were detected 42 and 49 nt upstream of the alpha-tubulin splice site and 58 nt upstream of the splice site in beta-tubulin. The regions surrounding these branch points lack homology to the consensus sequences determined for mammalian cells and yeasts; there is also no conservation among the sequences themselves. Thus, the identified sequences suggest that the mechanism of branch point recognition in T. brucei differs from the mechanism of recognition by U2 RNA that has been proposed for other eucaryotes.
Mol Cell Biol 1989 Oct
PMID:Mapping of branch sites in trans-spliced pre-mRNAs of Trypanosoma brucei. 247 24

In this paper we demonstrate that failure to complement between mutations at separate loci can be used to identify genes that encode interacting structural proteins. A mutation (nc33) identified because it failed to complement mutant alleles of the gene encoding the testis-specific beta 2-tubulin of Drosophila melanogaster (B2t) did not map to the B2t locus. We show that this second-site noncomplementing mutation is a missense mutation in alpha-tubulin that results in substitution of methionine in place of valine at amino acid 177. Because alpha- and beta-tubulin form a heterodimer, our results suggest that the genetic interaction, failure to complement, is based on the structural interaction between the protein products of the two genes. Although the nc33 mutation failed to complement a null allele of B2t (B2tn), a deletion of the alpha-tubulin gene to which nc33 mapped complemented B2tn. Thus, the failure to complement appears to require the presence of the altered alpha-tubulin encoded by the nc33 allele, which may act as a structural poison when incorporated into either the tubulin heterodimer or microtubules.
Mol Cell Biol 1989 Mar
PMID:Interacting proteins identified by genetic interactions: a missense mutation in alpha-tubulin fails to complement alleles of the testis-specific beta-tubulin gene of Drosophila melanogaster. 249 48

The ability of high doses of cortisol to retard the involution process in the rat ventral prostate was related to alterations in the pattern of gene expression. Poly(A)+ RNA preparations from the prostates of noncastrated, castrated, and castrated rats injected daily for 7 days with cortisol were compared by Northern blot hybridizations for the relative expression of genes associated with cell differentiation and maintenance (the C1 prostatic steroid binding protein gene and alpha-tubulin), with cell death (TRPM-2, hsp 70, and c-fos), and with hormone regulation (the androgen and glucocorticoid receptors). As anticipated, the concentration of C1 mRNA in the prostate fell to less than 4% of that in the noncastrated controls within 4 days after castration and was nearly undetectable after 7 days. This decline was retarded by cortisol treatment of 7-day castrated animals which sustained the level of C1 transcripts at approximately 50% of control. While the pattern of expression of alpha-tubulin indicated some minor fluctuations, with the highest level occurring 7 days after castration, the prostates of the cortisol-treated group had essentially the same concentration of this mRNA as the noncastrates. Cortisol also modified the expression of genes associated with prostatic cell death. The large increase in prostatic TRPM-2 mRNA, seen 7 days after castration, was reduced by over 80% after treatment with the glucocorticoid. Although not as abundantly expressed as TRPM-2, the castration-induced levels of transcripts for both hsp 70 and the protooncogene c-fos were substantially reduced by cortisol.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1989 Apr
PMID:Cortisol alters gene expression during involution of the rat ventral prostate. 249 51

Recent investigations have confirmed the presence of one alpha-tubulin gene (TUB1) and one beta-tubulin gene (TUB2) in the dimorphic fungus Histoplasma capsulatum. In the present study, Northern blot (RNA blot) analyses revealed multiple alpha-tubulin transcripts and a single beta-tubulin transcript in the yeast and mycelial phases of the high-virulence 217B strain and low-virulence Downs strain. S1 nuclease protection assays demonstrated one initiation start site and two major stop sites for the TUB1 transcripts, suggesting that variations in 3' processing generate the alpha-tubulin messages of 2.5 and 2.0 kilobases. Dot blot hybridization experiments indicated that tubulin gene expression is developmentally regulated during the dimorphic phase transitions. alpha- and beta-tubulin mRNAs increased six- to eightfold during the yeast-to-mycelium conversion and decreased two- to threefold during the reverse transition. These changes in tubulin mRNA content coincided with major morphological events associated with H. capsulatum development. Western blots (immunoblots) of H. capsulatum yeast-specific proteins resolved by two-dimensional gel electrophoresis demonstrated a single alpha- and a single beta-tubulin isoform. Multiple tubulin polypeptides expressed in mycelia are probably products of posttranslational modifications.
Mol Cell Biol 1989 May
PMID:Expression of alpha- and beta-tubulin genes during dimorphic-phase transitions of Histoplasma capsulatum. 254 58

To study the molecular aspects of the regulation of transcription of a multigene family, we have isolated and sequenced cDNA and genomic clones coding for the alpha-tubulin of the sea urchin Paracentrotus lividus. Two cDNA clones, P alpha 10 and P alpha 4, contain respectively the coding information for 391 C-terminal and for 338 N-terminal amino acids of the 452 residues that constitute the complete protein. They show silent nucleotide substitutions only, suggesting that P alpha 10 and P alpha 4 represent the cloned copies of two allelic gene transcripts, which encode for two alpha-tubulin isoforms with identical amino acid sequence in the region of the overlap. The comparison of the predicted amino acid sequence of the composite P alpha 4-10 and of the mouse M alpha-6 (Villasante et al., Mol Cell Biol 1986; 6:2409-2419) reveals a conservation of 97% between the two polypeptides. By RNA blotting hybridization six major alpha-tubulin transcripts were identified. Two, of 3.5 kb and 2.0 kb, are expressed in the unfertilized eggs and during early cleavage. The other two maternal mRNAs, of 2.4 kb and 1.8 kb, are expressed in both early and late cleavage embryos, but in the intestine the 1.8 kb RNA, which specifically reacted with the 3' specific probe of the P alpha 10 cDNA, is the only transcript detected. Finally, the 1.5 kb and 1.9 kb mRNAs represent the transcription of stage- and tissue-specific genes, respectively. In fact, the former becomes detectable at blastula stage and accumulates during late development, whereas the latter is found in the testis only. The sequence data of the 3' terminus of the alpha-3 genomic clone suggests that it encodes for a divergent alpha-tubulin, and it most probably corresponds to the testis-specific gene.
Mol Reprod Dev 1989
PMID:DNA sequence and pattern of expression of the sea urchin (Paracentrotus lividus) alpha-tubulin genes. 262 67

The consequences of altering the levels of alpha- and beta-tubulin in Saccharomyces cerevisiae were examined by constructing fusions of the structural genes encoding the tubulins to strong galactose-inducible promoters. Overexpression of beta-tubulin (TUB2) was lethal: cells arrested in the G2 stage of the cell cycle exhibited an increased frequency of chromosome loss, were devoid of microtubules, and accumulated beta-tubulin in a novel structure. Overexpression of the major alpha-tubulin gene (TUB1) was not lethal and did not affect chromosome segregation. The rate of alpha-tubulin mRNA and protein synthesis was increased, but the protein did not accumulate. Overexpression of both alpha- and beta-tubulin together resulted in arrested cell division, and cells accumulated excess tubules that contained both alpha- and beta-tubulin. Transient overexpression of both tubulins resulted in a high frequency of chromosome loss. These data suggest that strong selective pressure exists to prevent excess accumulation of microtubules or beta-tubulin and suggest a model by which this goal may be achieved by selective degradation of unassembled alpha-tubulin. Furthermore, the phenotype of beta-tubulin overexpression is similar to the phenotype of a beta-tubulin deficiency. These results add to a number of recent studies demonstrating that mutant phenotypes generated by overexpression can be informative about the function of the gene product.
Mol Cell Biol 1989 Mar
PMID:Dominant effects of tubulin overexpression in Saccharomyces cerevisiae. 265 85

Fragments of Physarum polycephalum DNA generated by partial digestion with Sau3A were cloned into phage-lambda EMBL4. A recombinant (phage-lambda E alpha Tu) containing an alpha-tubulin (E alpha-tubulin) gene was isolated. The E alpha-tubulin gene is part of the alt B locus. The gene was sequenced and was found to contain seven intervening sequences. The alpha-tubulin isotype (E alpha-tubulin) encoded by the gene has a methionine residue at the C-terminus. The E alpha-tubulin gene has much in common with the N alpha-tubulin gene cloned into phage-lambda NM1149 [M. J. Monteiro & R. A. Cox (1987) J. Mol. Biol. 193, 427-438]. However, the gene products E alpha-tubulin and N alpha-tubulin differ in amino acid sequence near to the C-terminus. E-peptide (corresponding to amino acids 440-448 of E alpha-tubulin) and N-peptide (corresponding to amino acids 437-445 of N alpha-tubulin) were synthesised and used to raise antibodies (E-antibodies and N-antibodies). The antibodies were used to show that on two-dimensional gel electrophoresis N alpha-tubulin travels to the alpha 1 position and E alpha-tubulin moves to the alpha 2 position. Gene-specific DNA probes were used to show that transcripts of the E alpha-tubulin gene were present in the plasmodial but not in the amoebal phase of the life cycle. The E- and N-antibodies detected E alpha- and N alpha-tubulins in plasmodia but not in amoebae, confirming that the expression of the E alpha- and N alpha-tubulin genes is regulated during development. E alpha- and N alpha-tubulin were shown to be components of spindle microtubules by indirect immunofluorescence microscopy.
 ...
PMID:Structure and expression of an alpha-tubulin gene of Physarum polycephalum. 265 44


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