UNIPROT:P51532 - FACTA Search

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Query: UNIPROT:P51532 (transcriptional activator)
6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The transcription of the majority of the ribosomal protein (rp) genes of Saccharomyces cerevisiae is activated by cis-acting elements, designated RPG boxes, which specifically bind the multifunctional protein RAP1 in vitro. To investigate to what extent this global system of transcription regulation has been conserved, we have isolated a number of rp genes of the related yeast species Kluyveromyces lactis and Kluyveromyces marxianus, whose counterparts in Saccharomyces are controlled by RAP1. The coding regions of these genes showed a sequence similarity of about 90% when compared to their Saccharomyces counterparts. In contrast, little or no sequence similarity was found between the upstream regions and the intervening sequences of Kluyveromyces and Saccharomyces homologs. However, the occurrence and the position of the introns is conserved. The sequence data also show that the physical linkage that exists in S. cerevisiae between the rp genes encoding RP59 (CRY1), S24 and L46 is conserved in Kluyveromyces. Northern analysis demonstrated that each of the isolated Kluyveromyces genes is transcriptionally active. By sequence comparison we identified a number of conserved sequences in the upstream region of each of the Kluyveromyces rp genes, which we designated the X, Z and RPGK boxes. The last one is highly similar, though not identical, to the S. cerevisiae RPG box. Functional analysis of the intergenic region between the genes encoding Kluyveromyces ribosomal proteins S24 and L46 showed that the RPGK box (+Z box) functions as a transcriptional activator, while the X box acts as a transcriptional repressor. Band-shift assays confirmed the existence of a RAP1-like protein in Kluyveromyces that binds to the RPGK box but not to the S. cerevisiae RPG box. In contrast, S. cerevisiae RAP1 did recognize the RPGK box.
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PMID:Structural and putative regulatory sequences of Kluyveromyces ribosomal protein genes. 148 69

The rate of ribosome formation in yeast is precisely adjusted to the physiological demands of the cell. During all growth conditions a balance is maintained in the production of all ribosomal constituents. Coordinate expression of the ribosomal protein (rp) genes is primarily accomplished at the transcriptional level. Transcription activation of the majority of the rp-genes is mediated through common upstream activating sequences, so-called RPG boxes, which occur usually in a tandem at a distance of 200-500 bp from the start codon. These RPG-boxes represent binding sites for a transcriptional activator, called TUF or RAP. The concentration of TUF parallels the cellular growth rate and evidence exists that the response of rp-genes upon nutritional changes is mediated by this factor. Recent findings indicate that TUF/RAP also activates other gene families involved in cellular growth rate. Furthermore, this multifunctional protein also binds to the mating-type silencer and telomeres in yeast. Some other rp-genes (e.g. those encoding S33 and L45) do not contain an RPG-box. They appear to be activated by another multifunctional protein, called ABF1 or SUF, by binding to another nucleotide motif. This multifunctional protein also activates other gene families, and in addition binds to the mating type silencer and ARS-elements.
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PMID:Coordinate expression of ribosomal protein genes in yeast as a function of cellular growth rate. 192 98

The GCN4 gene of the yeast Saccharomyces cerevisiae encodes a transcriptional activator of amino acid biosynthetic genes that is regulated at the translational level according to the availability of amino acids. GCN2 is a protein kinase required for increased translation of GCN4 mRNA in amino acid-starved cells. Centrifugation of cell extracts in sucrose gradients indicated that GCN2 comigrates with ribosomal subunits and polysomes. The fraction of GCN2 cosedimenting with polysomes was reduced under conditions in which polysomes were dissociated, suggesting that GCN2 is physically bound to these structures. When the association of 40S and 60S subunits was prevented by omitting Mg2+ from the gradient, almost all of the GCN2 comigrated with 60S ribosomal subunits, and it remained bound to these particles during gel electrophoresis under nondenaturing conditions. GCN2 could be dissociated from 60S subunits by 0.5 M KCl, suggesting that it is loosely associated with ribosomes rather than being an integral ribosomal protein. Accumulation of GCN2 on free 43S-48S particles and 60S subunits occurred during polysome runoff in vitro and under conditions of reduced growth rate in vivo. These observations, plus the fact that GCN2 shows preferential association with free ribosomal subunits during exponential growth, suggest that GCN2 interacts with ribosomes during the translation initiation cycle. The extreme carboxyl-terminal segment of GCN2 is essential for its interaction with ribosomes. These sequences are also required for the ability of GCN2 to stimulate GCN4 translation in vivo, leading us to propose that ribosome association by GCN2 is important for its access to substrates in the translational machinery or for detecting uncharged tRNA in amino acid-starved cells.
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PMID:Ribosome association of GCN2 protein kinase, a translational activator of the GCN4 gene of Saccharomyces cerevisiae. 203 14

The GCD2 protein is a translational repressor of GCN4, the transcriptional activator of multiple amino acid biosynthetic genes in Saccharomyces cerevisiae. We present evidence that GCD2 has a general function in the initiation of protein synthesis in addition to its gene-specific role in translational control of GCN4 expression. Two temperature-sensitive lethal gcd2 mutations result in sensitivity to inhibitors of protein synthesis at the permissive temperature, and the gcd2-503 mutation leads to reduced incorporation of labeled leucine into total protein following a shift to the restrictive temperature of 36 degrees C. The gcd2-503 mutation also results in polysome runoff, accumulation of inactive 80S ribosomal couples, and accumulation of at least one of the subunits of the general translation initiation factor 2 (eIF-2 alpha) in 43S-48S particles following a shift to the restrictive temperature. The gcd2-502 mutation causes accumulation of 40S subunits in polysomes, known as halfmers, that are indicative of reduced 40S-60S subunit joining at the initiation codon. These phenotypes suggest that GCD2 functions in the translation initiation pathway at a step following the binding of eIF-2.GTP.Met-tRNA(iMet) to 40S ribosomal subunits. consistent with this hypothesis, we found that inhibiting 40S-60S subunit joining by deleting one copy (RPL16B) of the duplicated gene encoding the 60S ribosomal protein L16 qualitatively mimics the phenotype of gcd2 mutations in causing derepression of GCN4 expression under nonstarvation conditions. However, deletion of RPL16B also prevents efficient derepression of GCN4 under starvation conditions, indicating that lowering the concentration of 60S subunits and reducing GCD2 function affect translation initiation at GCN4 in different ways. This distinction is in accord with a recently proposed model for GCN4 translational control in which ribosomal reinitiation at short upstream open reading frames in the leader of GCN4 mRNA is suppressed under amino acid starvation conditions to allow for increased reinitiation at the GCN4 start codon.
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PMID:GCD2, a translational repressor of the GCN4 gene, has a general function in the initiation of protein synthesis in Saccharomyces cerevisiae. 203 26

The DNA sequence UAST (TCGTTTTGTACGTTTTTCA) was found to mediate transcription of yeast ribosomal protein gene TCM1. UAST was defined as a transcriptional activator on the basis of loss of transcription accompanying deletions of all or part of UAST, orientation-independent restoration of transcription promoted by a synthetic UAST oligomer inserted either into TCM1 or into the yeast CYC1 gene lacking its transcriptional activation region, and diminished transcription following nucleotide alterations in UAST. UAST bound in vitro to a protein denoted TAF (TCM1 activation factor); TAF was concluded to be a transcriptional activator protein because nucleotide alterations in UAST that diminished transcription in vivo also diminished TAF binding in vitro. The sequence of UAST bore no obvious resemblance to UASrpg, the principal cis-acting element common to most yeast ribosomal protein genes. Likewise, TAF was distinguished from the UASrpg-binding protein TUF, since (i) TAF and TUF were chromatographically separable, (ii) binding of either TAF or TUF to its corresponding UAS was unaffected by an excess of UASrpg or UAST DNA, respectively, and (iii) photochemical cross-linking experiments showed that TAF was a protein of 147 kilodaltons (kDa), while TUF was detected as an approximately 120-kDa polypeptide, consistent with its known size. Cross-linking experiments also revealed that both UAST and UASrpg bound a second heretofore unobserved 82-kDa protein; binding of this additional protein appeared to require binding of TAF or TUF. On the basis of the biochemical characterization of TAF and a lack of sequence similarity between UAST and UASrpg, we suggest that transcription of TCM1 is mediated by a cis-acting sequence and at least one trans-acting factor different from the elements which promote transcription of most other ribosomal protein genes. A second trans-acting factor may be shared by TCM1 and other ribosomal protein genes; this factor could mediate coordinate regulation of these genes.
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PMID:Constitutive transcription of yeast ribosomal protein gene TCM1 is promoted by uncommon cis- and trans-acting elements. 305 14

The cDNA coding for the Xenopus laevis homolog of the transcriptional activator/repressor protein delta/YY1 was isolated from a lambda gt11 oocyte cDNA library. The deduced aminoacid sequence shows that the four zinc fingers of the DNA binding domain are 99% conserved when compared to the mouse (delta) and 95% to the human (YY1) proteins, while differences are found in the N-terminal region. In particular, the long run of consecutive glycines and histidines of delta and YY1 is missing. The protein, named FIII/YY1, was overexpressed into Xenopus oocytes from the cDNA under direction of the L14 rp-promoter and found to share antigenic and DNA-binding properties with the oocyte endogenous protein binding to the first exon of the X.laevis ribosomal protein genes (rp-genes) L1 and L14.
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PMID:Characterization of FIII/YY1, a Xenopus laevis conserved zinc-finger protein binding to the first exon of L1 and L14 ribosomal protein genes. 780 55

The lemA gene of Pseudomonas syringae pv. syringae encodes the sensor kinase of a bacterial two-component signal transduction system. Phenotypes that are lemA dependent in P. syringae include lesion formation on bean and production of extracellular protease and the antibiotic syringomycin. Recently, the gacA gene has been identified as encoding the response regulator of the lemA regulon. To identify additional components that interact with LemA, suppressors of a lemA mutation were sought. A locus was identified that, when present in multiple copies, restores extracellular protease production to a lemA insertion mutant of P. syringae pv. syringae. This locus was found to encode the P. syringae homologs of translation initiation factor IF3 and ribosomal proteins L20 and L35 of Escherichia coli and other bacteria. Deletion analysis and data from Western immunoblots with anti-IF3 antiserum suggest that protease restoration does not require IF3. Deletion of both the L35 and L20 genes resulted in loss of protease restoration, whereas disruption of either gene alone increased protease restoration. Our results suggest that overexpression of either L20 or L35 is sufficient for protease restoration. It is unclear how alteration of ribosomal protein expression compensates in this instance for loss of a transcriptional activator, but a regulatory role for L20 and L35 apart from their function in the ribosome may be indicated.
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PMID:Suppression of a sensor kinase-dependent phenotype in Pseudomonas syringae by ribosomal proteins L35 and L20. 862 80

We have previously shown that a functional secretory pathway is essential for continued ribosome synthesis in Saccharomyces cerevisiae. When a temperature-sensitive mutant defective in the secretory pathway is transferred to the non-permissive temperature, transcription of both rRNA genes and ribosomal protein genes is nearly abolished. In order to define the cis -acting element(s) of ribosomal protein genes sensitive to a defect in the secretory pathway, we have constructed a series of fusion genes containing the CYH2 promoter region, with various deletions, fused to lacZ. Each fusion gene for which transcription is detected is subject to the repression. Rap1p is the transcriptional activator for most ribosomal protein genes, as well as having an important role in silencing in the vicinity of telomeres and at the silent mating-type loci. To assess its role in the repression of transcription by the defect in the secretory pathway, we have introduced rap1 mutations. The replacement of wild-type Rap1p by Rap1p truncated at the C-terminal region caused substantial attenuation of the repression. Furthermore, we have demonstrated that the Rap1p-truncation affects the repression of TCM1 , encoding ribosomal protein L3, which has no Rap1p-binding site in its upstream regulatory region. These results suggest that the repression of transcription of ribosomal protein genes by a secretory defect is mediated through Rap1p, but does not require a Rap1p-binding site within the UAS.
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PMID:The C-terminal silencing domain of Rap1p is essential for the repression of ribosomal protein genes in response to a defect in the secretory pathway. 946 69

Growth of Saccharomyces cerevisiae requires coordination of cell cycle events (e.g., new cell wall deposition) with constitutive functions like energy generation and duplication of protein mass. The latter processes are stimulated by the phosphoprotein Gcr1p, a transcriptional activator that operates through two different Rap1p-mediated mechanisms to boost expression of glycolytic and ribosomal protein genes, respectively. Simultaneous disruption of both mechanisms results in a loss of glucose responsiveness and a dramatic drop in translation rate. Since a critical rate of protein synthesis (CRPS) is known to mediate passage through Start and determine cell size by modulating levels of Cln3p, we hypothesized that GCR1 regulates cell cycle progression by coordinating it with growth. We therefore constructed and analyzed gcr1delta cln3delta and gcr1delta cln1delta cln2delta strains. Both strains are temperature and cold sensitive; interestingly, they exhibit different arrest phenotypes. The gcr1delta cln3delta strain becomes predominantly unbudded with 1N DNA content (G1 arrest), whereas gcr1delta cln1delta cln2delta cells exhibit severe elongation and apparent M phase arrest. Further analysis demonstrated that the Rap1p/Gcr1p complex mediates rapid growth in glucose by stimulating both cellular metabolism and CLN transcription.
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PMID:The global transcriptional activator of Saccharomyces cerevisiae, Gcr1p, mediates the response to glucose by stimulating protein synthesis and CLN-dependent cell cycle progression. 1466 61

Ribosome biogenesis drives cell growth, and the large transcriptional output underlying this process is tightly regulated. The Target of Rapamycin (TOR) kinase is part of a highly conserved signaling pathway linking nutritional and stress signals to regulation of ribosomal protein (RP) and ribosome biogenesis (Ribi) gene transcription. In Saccharomyces cerevisiae, one of the downstream effectors of TOR is Sfp1, a transcriptional activator that regulates both RP and Ribi genes. Here, we report that Sfp1 interacts directly with TOR complex 1 (TORC1) in a rapamycin-regulated manner, and that phosphorylation of Sfp1 by this kinase complex regulates its function. Sfp1, in turn, negatively regulates TORC1 phosphorylation of Sch9, another key TORC1 target that acts in parallel with Sfp1, revealing a feedback mechanism controlling the activity of these proteins. Finally, we show that the Sfp1-interacting protein Mrs6, a Rab escort protein involved in membrane trafficking, regulates both Sfp1 nuclear localization and TORC1 signaling.
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PMID:Sfp1 interaction with TORC1 and Mrs6 reveals feedback regulation on TOR signaling. 1932 65

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