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At least 1,621 records · Page 90Linked to original sources
PubMed2001

Identification of the G13 (cAMP-response-element-binding protein-related protein) gene product related to activating transcription factor 6 as a transcriptional activator of the mammalian unfolded protein response.

Eukaryotic cells control the levels of molecular chaperones and folding enzymes in the endoplasmic reticulum (ER) by a transcriptional induction process termed the unfolded protein response (UPR). The mammalian UPR is mediated by the cis-acting ER stress response element consisting of 19 nt (CCAATN(9)CCACG), the CCACG part of which is considered to provide specificity. We recently identified the basic leucine zipper (bZIP) protein ATF6 as a mammalian UPR-specific transcription factor; ATF6 is activated by ER stress-induced proteolysis and binds directly to CCACG. Here we report that eukaryotic cells express another bZIP protein closely related to ATF6 in both structure and function. This protein encoded by the G13 (cAMP response element binding protein-related protein) gene is constitutively synthesized as a type II transmembrane glycoprotein anchored in the ER membrane and processed into a soluble form upon ER stress as occurs with ATF6. The proteolytic processing of ATF6 and the G13 gene product is accompanied by their relocation from the ER to the nucleus; their basic regions seem to function as a nuclear localization signal. Overexpression of the soluble form of the G13 product constitutively activates the UPR, whereas overexpression of a mutant lacking the activation domain exhibits a strong dominant-negative effect. Furthermore, the soluble forms of ATF6 and the G13 gene product are unable to bind to several point mutants of the cis-acting ER stress response element in vitro that hardly respond to ER stress in vivo. We thus concluded that the two related bZIP proteins are crucial transcriptional regulators of the mammalian UPR, and propose calling the ATF6 gene product ATF6alpha and the G13 gene product ATF6beta.

Activating Transcription Factor 6↗
PubMed1998

Transcriptional and post-transcriptional regulation by nickel of sodN gene encoding nickel-containing superoxide dismutase from Streptomyces coelicolor Müller.

A novel type of superoxide dismutase containing nickel as a cofactor (NiSOD) has been discovered in several Streptomyces spp. The gene for NiSOD (sodN) was cloned from S. coelicolor Müller using degenerate oligonucleotide probes designed from the N-terminal peptide sequence of the purified enzyme. It encodes a polypeptide of 131 amino acids (14703 Da), without any apparent sequence similarity to other known proteins. The N-terminus of the purified NiSOD was located 14 amino acids downstream from the initiation codon of the deduced open reading frame (ORF), indicating the involvement of protein processing. The molecular mass of the processed polypeptide was predicted to be 13201 Da, in close agreement with that of the purified NiSOD (13.4 kDa). The transcription start site of the sodN gene was determined by S1 mapping and primer extension analysis. Ni2+ regulates the synthesis of NiSOD polypeptide. S1 mapping of both 5' and 3' ends of sodN mRNA revealed that Ni2+ increased the level of monocistronic sodN mRNA by more than ninefold without changing its half-life, thus demonstrating that Ni2+ regulates transcription. Both precursor and processed NiSOD polypeptides with little SOD activity were produced from the cloned sodN gene in S. lividans in the absence of sufficient Ni2+; however, on addition of Ni2+, active NiSOD consisting of only processed polypeptide was formed. Expression of the full-length sodN gene in E. coli produced NiSOD polypeptide without any SOD activity even in the presence of Ni2+. However, deletion of nucleotides encoding the N-terminal 14 amino acids from the sodN gene allowed the production of active NiSOD in E. coli, indicating that N-terminal processing is required to produce active NiSOD. These results reveal the unique role of nickel as a multifaceted regulator in S. coelicolor controlling sodN transcription and protein processing, as well as acting as a catalytic cofactor.

Amino Acid Sequence↗
PubMed1998

Negative transcriptional regulation of a positive regulator: the expression of malT, encoding the transcriptional activator of the maltose regulon of Escherichia coli, is negatively controlled by Mlc.

The maltose regulon consists of 10 genes encoding a multicomponent and binding protein-dependent ABC transporter for maltose and maltodextrins as well as enzymes necessary for the degradation of these sugars. MalT, the transcriptional activator of the system, is necessary for the transcription of all mal genes. MalK, the energy-transducing subunit of the transport system, acts phenotypically as repressor, particularly when overproduced. We isolated an insertion mutation that strongly reduced the repressing effect of overproduced MalK. The affected gene was sequenced and identified as mlc, a known gene encoding a protein of unknown function with homology to the Escherichia coli NagC protein. The loss of Mlc function led to a threefold increase in malT expression, and the presence of mlc on a multicopy plasmid reduced malT expression. By DNasel protection assay, we found that Mlc protected a DNA region comprising positions +1 to +23 of the malT transcriptional start point. Using a mlc-lacZ fusion in a mlc and mlc+ background, we found that Mlc represses its own expression. As Mlc also regulates another operon (manXYZ, see pages 369-379 of this issue), it may very well constitute a new global regulator of carbohydrate utilization.

ATP-Binding Cassette Transporters↗
PubMed2000

Novel fungal transcriptional activators, Cmr1p of Colletotrichum lagenarium and pig1p of Magnaporthe grisea, contain Cys2His2 zinc finger and Zn(II)2Cys6 binuclear cluster DNA-binding motifs and regulate transcription of melanin biosynthesis genes in a developmentally specific manner.

Colletotrichum lagenarium and Magnaporthe grisea are plant pathogenic fungi that produce melanin during the appressorial differentiation stage of conidial germination and during the late stationary phase of mycelial growth. Here, we report the identification of genes for two unique transcription factors, CMR1 (Colletotrichum melanin regulation) and PIG1 (pigment of Magnaporthe), that are involved in melanin biosynthesis. Both Cmr1p and Pig1p contain two distinct DNA-binding motifs, a Cys2His2 zinc finger motif and a Zn(II)2Cys6 binuclear cluster motif. The presence of both these motifs in a single transcriptional regulatory protein is unique among known eukaryotic transcription factors. Deletion of CMR1 in C. lagenarium caused a defect in mycelial melanization, but not in appressorial melanization. Also, cmr1Delta mutants do not express the melanin biosynthetic structural genes SCD1 and THR1 during mycelial melanization, although the expression of these two genes was not affected during appressorial melanization.

Amino Acid Motifs↗
PubMed2002

Differential regulation of TGA transcription factors by post-transcriptional control.

Transcription factors often belong to multigene families and their individual contribution in a particular regulatory network remains difficult to assess. We show here that specific members from a family of conserved Arabidopsis bZIP transcription factors, the TGA proteins, are regulated in their protein stability by developmental stage-specific proteolysis. Using GFP fusions of three different Arabidopsis TGA factors that represent members of distinct subclasses of the TGA factor family, we demonstrate that two of these TGA proteins are specifically targeted for proteolysis in mature leaf cells. Using a supershift gel mobility assay, we found evidence for similar regulation of the cognate proteins as compared to the GFP fusion proteins expressed under the cauliflower mosaic virus (CaMV) 35S promoter. Using various inhibitors, we showed that the expression of at least one of these three TGA factors could be stabilized by inhibition of proteasome-mediated proteolysis. This study indicates that TGA transcription factors may be regulated by distinct pathways of targeted proteolysis that can serve to modulate the contribution of specific members of a multigene family in complex regulatory pathways.

Arabidopsis↗
PubMed1999

Induction of ferritin and heat shock proteins by prostaglandin A1 in human monocytes. Evidence for transcriptional and post-transcriptional regulation.

Prostaglandins of the A type (PGA) exert a cytoprotective activity during hyperthermia and virus infection. This effect is associated with induction of heat shock proteins (HSP) in mammalian cells. We now report that, in human monocytes, PGA1 is able to induce the synthesis of the iron-binding, redox-regulated protein ferritin. L-chain ferritin induction is consequent to a substantial increase in the accumulation of L-chain ferritin transcripts in PGA1-treated cells, whereas H-chain ferritin is regulated post-transcriptionally, consequently to reduction of iron-regulatory protein binding to iron-responsive elements in ferritin mRNA. Ferritin induction is specific for cyclopentenone prostaglandins (PGA1, PGA2, PGJ2, Delta12-PGJ2), whereas other arachidonic acid (AA) metabolites have no effect. In human monocytes, PGA1 also induces heat shock gene transcription via heat shock factor activation, as well as the synthesis of the oxidative-stress protein heme oxygenase (HOS). Differently from HSP, the induction of ferritin by PGA1 is specific for monocytes. Monocytes/macrophages play a pivotal role in inflammation, controlling iron metabolism and releasing a variety of mediators, including proinflammatory reactive oxygen species (ROS), cytokines and AA metabolites. As ferritin, together with hsp70 and HO, plays a key role in protection from oxidant damage, these results suggest that PGA1 may have cytoprotective activity also during oxidative injury.

Arachidonic Acid↗
PubMed2000

Interaction of expanded polyglutamine stretches with nuclear transcription factors leads to aberrant transcriptional regulation in polyglutamine diseases.

At least eight inherited neurodegenerative diseases are known to be caused by expanded CAG repeats encoding polyglutamine (polyQ) stretches. Although cytotoxicities of expanded polyQ stretches have been suggested, the molecular mechanisms of neurodegeneration remain unclear. The nuclear translocation of mutant proteins containing expanded polyQ stretches has been demonstrated as a prerequisite for the expression of their cytotoxicity. Hypothesizing that nuclear proteins that interact with mutant proteins, particularly, those that bind to the expanded polyQ stretches, are involved in the pathogenetic mechanisms underlying neurodegeneration, nuclear proteins were screened for their capability of binding to expanded polyQ stretches. It was found that expanded polyQ stretches preferentially bind to TAF(II)130, a coactivator involved in cAMP-responsive element-binding protein (CREB)-dependent transcriptional activation. The binding of TAF(II)130 with expanded polyQ stretches strongly suppresses CREB-dependent transcriptional activation, suggesting that interference with transcription due to the binding of expanded polyQ stretches with TAF(II)130 and redistribution of TAF(II)130 are involved in the pathogenetic mechanisms underlying neurodegeneration.

Animals↗
PubMed2000

Characterization of a transcription factor binding site, specifically activating MIA transcription in melanoma.

We have previously isolated the protein MIA, which is secreted from melanoma cells, and identified highly restricted expression patterns in melanocytic tumors. Preliminary studies of the human MIA gene provided evidence that the promoter is specifically activated in melanoma cells but is silent in nonmelanocytic cells and benign melanocytes. In this study we aimed to identify cis-regulatory promoter elements that mediate promoter activation during malignant transformation of melanocytes. We therefore subcloned 1.4 kb of the murine MIA promoter and a series of 5' deletion constructs into a luciferase reporter plasmid and identified the most active cis-regulatory element between nucleic acids -230 and -130. Cloning oligomeric fragments of this promoter region in front of a minimal TK promoter revealed a 30 bp enhancer element mediating expression of the reporter gene in melanoma cells but not in melanocytes or nonmelanocytic cells. Gel mobility shift assays and southwestern blots led to the identification of specific DNA-protein complexes in melanoma cells. Fine mutational analysis of the cis-regulatory promoter element showed that two critical nucleic acid residues are essential for both transcriptional activity and formation of the band shift complexes. By an initial small-scale affinity purification we were able to isolate a protein approximately 32 kDa in size from melanoma cells, which we refer to as MATF ("melanoma-associated transcription factor"). Our study identified for the first time MATF, a transcription factor that is upregulated or activated during malignant transformation of melanocytes.

3T3 Cells↗
PubMed2001

TH2 cytokine-associated transcription factors in atopic and nonatopic asthma: evidence for differential signal transducer and activator of transcription 6 expression.

BACKGROUND: The expression of IL-4 and IL-5 is increased in patients with atopic asthma compared with control subjects and correlates with indices of pulmonary function. In nonatopic asthma the expression of IL-4, unlike IL-5, fails to correlate with pulmonary function, and compared with their atopic counterparts, these patients have fewer cells expressing IL-4 receptor (IL-4R). As such, a deficiency in the IL-4 signaling pathway may be implicated in nonatopic asthma. The transcription factors GATA-3 and cMAF mediate IL-4 and IL-5 synthesis, whereas signal transducer and activator of transcription 6 (STAT-6) is critical for IL-4R signaling. OBJECTIVE: This study examines the expression profile of these transcription factors in asthma, according to atopic status. METHODS: With immunocytochemistry, the expression of GATA-3, cMAF, and STAT-6 protein was determined in sections of bronchial biopsy specimens from patients with atopic asthma (n = 7), patients with nonatopic asthma (n = 8), and control subjects (n = 8). RESULTS: Higher numbers of cells expressing GATA-3 and cMAF were observed in patients with atopic and those with nonatopic asthma than in control subjects and patients with tuberculosis (P <.001). There were also more STAT-6-immunoreactive cells in patients with atopic and those with nonatopic asthma than in control subjects (P <.0001, P <.05). Notably, however, fewer cells expressing STAT-6 protein were observed in nonatopic versus atopic asthma (P <.0001). CONCLUSIONS: These results demonstrate the upregulation of GATA-3 and cMAF in both variants of asthma and indicate that reduced IL-4R signaling, because of lower STAT-6 expression, may be a feature of nonatopic asthma.

Adult↗
PubMed2004

Transcriptional switch by activating transcription factor 2-derived peptide sensitizes melanoma cells to apoptosis and inhibits their tumorigenicity.

The notorious resistance of melanoma cells to drug treatment can be overcome by expression of a 50-aa peptide derived from activating transcription factor 2 (ATF2(50-100)). Here we demonstrate that ATF2(50-100) induced apoptosis by sequestering ATF2 to the cytoplasm, thereby inhibiting its transcriptional activities. Furthermore, ATF2(50-100) binds to c-Jun N-terminal kinase (JNK) and increases its activity. Mutation within ATF2(50-100) that impairs association with JNK and the inhibition of JNK or c-Jun expression by RNA interference (RNAi) reduces the degree of ATF2(50-100)-induced apoptosis. In contrast, TAM67, a dominant negative of the Jun family of transcription factors, or JunD RNAi attenuates sensitization of melanoma cells expressing ATF2(50-100) to apoptosis after treatment with anisomycin, which is used as a model drug. Mutations within the JNK binding region of ATF2(50-100) or expression of TAM67 or JunD RNAi attenuates inhibition of melanoma's tumorigenicity by ATF2(50-100). We conclude that inhibition of ATF2 in concert with increased JNK/Jun and JunD activities is central for the sensitization of melanoma cells to apoptosis and inhibition of their tumorigenicity.

Activating Transcription Factor 2↗
PubMed2006

Transcriptional and posttranscriptional regulation of transcription factor expression in Arabidopsis roots.

Understanding how the expression of transcription factor (TF) genes is modulated is essential for reconstructing gene regulatory networks. There is increasing evidence that sequences other than upstream noncoding can contribute to modulating gene expression, but how frequently they do so remains unclear. Here, we investigated the regulation of TFs expressed in a tissue-enriched manner in Arabidopsis roots. For 61 TFs, we created GFP reporter constructs driven by each TF's upstream noncoding sequence (including the 5'UTR) fused to the GFP reporter gene alone or together with the TF's coding sequence. We compared the visually detectable GFP patterns with endogenous mRNA expression patterns, as defined by a genome-wide microarray root expression map. An automated image analysis method for quantifying GFP signals in different tissues was developed and used to validate our visual comparison method. From these combined analyses, we found that (i) the upstream noncoding sequence was sufficient to recapitulate the mRNA expression pattern for 80% (35/44) of the TFs, and (ii) 25% of the TFs undergo posttranscriptional regulation via microRNA-mediated mRNA degradation (2/24) or via intercellular protein movement (6/24). The results suggest that, for Arabidopsis TFs, upstream noncoding sequences are major contributors to mRNA expression pattern establishment, but modulation of transcription factor protein expression pattern after transcription is relatively frequent. This study provides a systematic overview of regulation of TF expression at a cellular level.

Arabidopsis↗
PubMed1993

Transcription factors NF-IL6 and NF-kappa B synergistically activate transcription of the inflammatory cytokines, interleukin 6 and interleukin 8.

Single binding sites for transcription factors NF-IL6 and NF-kappa B are present in the promoter of the interleukin (IL) 6 gene. Previous studies of internally deleted promoter mutants demonstrated that these two sites are important for the transcriptional regulation of this gene. In this report, we describe the synergistic activation of the IL-6 promoter by transcription factors NF-IL6 and NF-kappa B. Cotransfection of NF-IL6 with the NF-kappa B p65 subunit resulted in strong synergistic activation of an IL-6 promoter-reporter construct. Both the NF-IL6 and NF-kappa B binding sites in the IL-6 promoter were required for synergistic activation. Similar synergistic activation was observed in the IL-8 promoter, which also contains both NF-IL6 and NF-kappa B binding sites. Furthermore, we demonstrated that NF-IL6 and the NF-kappa B p65 subunit directly associated via the basic leucine-zipper domain of NF-IL6 and the Rel homology domain of p65. Since the promoters of many other genes involved in the inflammatory and acute-phase responses also contain binding sites for NF-IL6 and NF-kappa B, the cooperation between these two factors may have an important role in these responses. We also discuss the possible interplay between various viral gene products and these two factors in the process of viral infection and constitutive cytokine production.

Base Sequence↗
PubMed1995

Spacing of palindromic half sites as a determinant of selective STAT (signal transducers and activators of transcription) DNA binding and transcriptional activity.

Signal transducers and activators of transcription (STAT proteins) bind to palindromic sequence elements related to interferon gamma (IFN-gamma) activation sites, which were first identified in the promoters of IFN-gamma-inducible genes. Although the sequences of the natural palindromic STAT-binding elements vary considerably, they conform to the general structure TT(N)5AA. We have systematically examined the effects of the spacing between the TT and AA core half sites on the binding of the STAT complexes activated by IFN-gamma, interleukin (IL) 6, granulocyte-macrophage colony-stimulating factor, and IL-4. We show that (i) as suggested earlier, a core palindromic TT--AA motif with a 5-bp spacing displays general STAT binding, (ii) a palindromic motif with a spacing of 4 bp selectively binds to complexes containing Stat3, and (iii) a motif with a 6-bp spacing selectively binds the STAT complexes activated by IL-4. We have examined natural elements in the promoters of cytokine-responsive genes that differ in half-site spacing and found that they display binding properties predicted from the synthetic binding sites. Furthermore, the observed differential selective binding characteristics for the most part correlate with the ability to mediate transcriptional activation of transfected test genes in response to the cytokines tested. Our results thus demonstrate that the specificity of STAT-directed transcription in response to particular cytokines or cytokine families depends in part on the spacing of half sites within the conserved response element sequence.

Base Sequence↗
PubMed1996

STAT3beta, a splice variant of transcription factor STAT3, is a dominant negative regulator of transcription.

The 89-kDa STAT3 protein is a latent transcription factor which is activated in response to cytokines (interleukin (IL)-5 and -6) and growth factors (epidermal growth factor). Binding of IL-5 to its specific receptor activates JAK2 which leads to the tyrosine phosphorylation of STAT3 proteins. Here we report the cloning of a cDNA encoding a variant of the transcription factor STAT3 (named STAT3beta) which was isolated by screening an eosinophil cDNA library. Compared to wild-type STAT3, STAT3beta lacks an internal domain of 50 base pairs located near the C terminus. This splice product is a naturally occurring isoform of STAT3 and encodes a 80-kDa protein. We found by reconstitution of the human IL-5R in COS cells that like STAT3, STAT3beta is phosphorylated on tyrosine and binds to the pIRE from the ICAM-1 promoter after IL-5 stimulation. However, STAT3beta fails to activate a pIRE containing promoter in transient transfection assays. Instead, co-expression of STAT3beta inhibits the transactivation potential of STAT3. These results suggests that STAT3beta functions as a negative regulator of transcription.

Amino Acid Sequence↗
PubMed1996

Plasminogen activator inhibitor type 2 gene induction by tumor necrosis factor and phorbol ester involves transcriptional and post-transcriptional events. Identification of a functional nonameric AU-rich motif in the 3'-untranslated region.

Plasminogen activator inhibitor type 2 (PAI-2) mRNA and antigen levels are synergistically induced in HT-1080 fibrosarcoma cells when treated with a combination of tumor necrosis factor (TNF) and phorbol 12-myristate 13-acetate (PMA). Here we demonstrate that this effect is not fully reflected at the level of gene transcription, suggesting a contribution of post-transcriptional events in this induction. Insertion of the 3'-untranslated region (3'-UTR) of PAI-2 mRNA into the 3'-UTR of a rabbit beta-globin reporter gene reduces beta-globin-PAI-2 chimeric mRNA expression in stably transfected cells. The region within the PAI-2 3'-UTR responsible for this effect is located within the 368-nucleotide sequence preceding the poly(A) tail, a segment that includes a nonameric UUAUUUAUU motif. Mutagenesis of this element abolishes the PAI-2 3'-UTR destabilizing effect, revealing a functional role for this motif. TNF and PMA co-treatment of transfected cells increases beta-globin-PAI-2 chimeric mRNA expression 3-4-fold, indicating that the inherently unstable 3'-UTR of PAI-2 mRNA can become stabilized in response to TNF and PMA. Our results indicate that induction of PAI-2 gene expression by TNF and PMA involves both direct transcription as well as mRNA stabilization, the latter involving an AU-rich nonameric motif in the 3'-UTR.

Animals↗
PubMed1997

Hepatitis B virus X protein is a transcriptional modulator that communicates with transcription factor IIB and the RNA polymerase II subunit 5.

Hepatitis B virus X protein (HBx) transactivates viral and cellular genes through a wide variety of cis-elements. However, the mechanism is still obscure. Our finding that HBx directly interacts with RNA polymerase II subunit 5 (RPB5), a common subunit of RNA polymerases, implies that HBx directly modulates the function of RNA polymerase (Cheong, J. H., Yi, M., Lin, Y., and Murakami, S. (1995) EMBO J. 14, 142-150). In this context, we examined the possibility that HBx and RPB5 interact with other general transcription factors. HBx and RPB5 specifically bound to transcription factor IIB (TFIIB) in vitro, both of which were detected by either far-Western blotting or the glutathione S-transferase-resin pull-down assay. Delineation of the binding regions of these three proteins revealed that HBx, RPB5, and TFIIB each has two binding regions for the other two proteins. Co-immunoprecipitation using HepG2 cell lysates that express HBx demonstrated trimeric interaction in vivo. Some HBx substitution mutants, which had severely impaired transacting activity, exhibited reduced binding affinity with either TFIIB or RPB5 in a mutually exclusive manner, suggesting that HBx transactivation requires the interactions of both RPB5 and TFIIB. These results indicated that HBx is a novel virus modulator that facilitates transcriptional initiation by stabilizing the association between RNA polymerase and TFIIB through communication with RPB5 and TFIIB.

Gene Expression Regulation, Viral↗
PubMed1997

The p38/reactivating kinase mitogen-activated protein kinase cascade mediates the activation of the transcription factor insulin upstream factor 1 and insulin gene transcription by high glucose in pancreatic beta-cells.

Insulin upstream factor 1 (IUF1), a transcription factor present in pancreatic beta-cells, binds to the sequence C(C/T)TAATG present at several sites within the human insulin promoter. Here we isolated and sequenced cDNA encoding human IUF1 and exploited it to identify the signal transduction pathway by which glucose triggers its activation. In human islets, or in the mouse beta-cell line MIN6, high glucose induced the binding of IUF1 to DNA, an effect mimicked by serine/threonine phosphatase inhibitors, indicating that DNA binding was induced by a phosphorylation mechanism. The glucose-stimulated binding of IUF1 to DNA and IUF1-dependent gene transcription were both prevented by SB 203580, a specific inhibitor of stress-activated protein kinase 2 (SAPK2, also termed p38 mitogen-activated protein kinase, reactivating kinase, CSBP, and Mxi2) but not by several other protein kinase inhibitors. Consistent with this finding, high glucose activated mitogen-activated protein kinase-activated protein kinase 2 (MAPKAP kinase-2) (a downstream target of SAPK2) in MIN6 cells, an effect that was also blocked by SB 203580. Cellular stresses that trigger the activation of SAPK2 and MAPKAP kinase-2 (arsenite, heat shock) also stimulated IUF1 binding to DNA and IUF1-dependent gene transcription, and these effects were also prevented by SB 203580. IUF1 expressed in Escherichia coli was unable to bind to DNA, but binding was induced by incubation with MgATP, SAPK2, and a MIN6 cell extract, which resulted in the conversion of IUF1 to a slower migrating form. SAPK2 could not be replaced by p42 MAP kinase, MAPKAP kinase-2, or MAPKAP kinase-3. The glucose-stimulated activation of IUF1 DNA binding and MAPKAP kinase-2 (but not the arsenite-induced activation of these proteins) was prevented by wortmannin and LY 294002 at concentrations similar to those that inhibit phosphatidylinositide 3-kinase. Our results indicate that high glucose (a cellular stress) activates SAPK2 by a novel mechanism in which a wortmannin/LY 294002-sensitive component plays an essential role. SAPK2 then activates IUF1 indirectly by activating a novel IUF1-activating enzyme.

Amino Acid Sequence↗
PubMed1997

Analysis of post-transcriptional regulation operating on transcription products of the tandemly linked Leishmania infantum hsp70 genes.

The genomic organization and expression of the hsp70 genes of Leishmania infantum were examined. In the cluster there are at least six copies of the hsp70 genes arranged in a head-to-tail tandem of 3. 8-kilobase repetition units. The hsp70 gene copy (gene 6) located at the 3' end of the tandem has a 3'-untranslated region highly divergent in sequence relative to the 3'-untranslated region of the rest of hsp70 gene copies (genes 1-5). Nuclease S1 protection assays indicated that the steady-state level of the mRNAs derived from gene 6 is about 50-fold more abundant than the transcript level derived from genes 1-5. Nuclear run-on assays showed, however, that all hsp70 genes are transcribed at similar rates. Thus, it is likely that the differences in the steady-state levels of the transcripts from the hsp70 genes should be associated with variations in their processing or maturation rates. While the abundance of the mRNAs derived from hsp70 genes 1-5 is increased by heat shock, the hsp70 gene 6 mRNA level remains unaffected. Our data showed that ongoing protein synthesis is required for the maintenance of the heat inducement, depicting, thus, a post-transcriptional mechanism of positive regulation involving a labile protein factor that would be either induced or activated during heat shock.

Animals↗