Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cucumber mosaic virus (CMV)-encoded 2b protein has been implicated to play a role in long distance movement of the virus through the plant's transport system. It is unknown, however, how it mediates virus movement and whether any intrinsic components of plant cells also participate in this process. To isolate a host factor that interacts with 2b, the yeast two-hybrid system was used. First, it was found that the 2b protein per se could function as a transcriptional activator in yeast. However, its two carboxyl terminal deletion mutants, 2bdelta98 and 2bdelta95, which lacked 12 and 15 amino acids from the carboxyl terminus respectively, showed complete absence of transcriptional activation in yeast. A tobacco cDNA library expressing the GAL4 activation domain fusion proteins was screened using 2bdelta98 as a bait. A clone named 2bip (2b-interacting protein) was isolated whose translation product apparently interacted with 2b. Consistent with this observation, bacterially expressed GST-2bip fusion protein bound tightly to 2bdelta95 and 2bdelta98 polypeptides in vitro, as well as to the unmodified 2b protein. Nucleotide sequencing and database searches revealed that the amino acid sequence deduced from it was similar to a prokaryotic LytB protein and an unknown protein of Arabidopsis. DNA and RNA gel blot analyses showed that 2bip-related sequences were present in the tobacco genome and that transcripts corresponding to 2bip were expressed constitutively in various plant organs and in response to CMV infection. These results suggest 2bip as a novel host factor that is capable of interacting with CMV2b.
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PMID:Isolation of a putative tobacco host factor interacting with cucumber mosaic virus-encoded 2b protein by yeast two-hybrid screening. 1059 45

The retroviral oncoprotein v-Rel is a transcriptional activator in the Rel/NF-kappaB family of eukaryotic transcription factors. v-Rel malignantly transforms a variety of cell types in vitro and in vivo, and its transforming activity is dependent on the ability of v-Rel to bind to DNA and activate transcription. In this report, we used the yeast two-hybrid assay to identify proteins that interact with C-terminal sequences of v-Rel that are needed for transcriptional activation and transformation. One protein, Trip6, that we identified in this screen was previously identified as a thyroid hormone receptor-interacting protein. Trip6 is a member of a subfamily of LIM domain-containing proteins that are thought to transport intracellular signals from the cell surface to the nucleus. By several criteria, we show that sequences from Trip6, which include the LIM domains, behave as a coactivator for transcriptional activation by v-Rel. That is, a GAL4-Trip6 fusion protein can activate transcription in yeast and chicken cells, Trip6 can enable C-terminal sequences of v-Rel to activate transcription in yeast, and Trip6 can enhance activation by v-Rel from a kappaB site reporter plasmid in yeast. Although full-length Trip6 localizes to adhesion plaques, deletion of N-terminal sequences allows human Trip6 to enter the nucleus of chicken cells. Lastly, Northern blotting shows that Trip6 mRNA is expressed in many human tissues. Coexpression of Trip6 does not affect the transforming activity of v-Rel. Taken together, our results indicate that Trip6 may be a protein that is important for the ability of v-Rel to activate transcription and transform cells, and may represent a potential target for blocking Rel-mediated oncogenesis and transcriptional activation.
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PMID:LIM domain-containing protein trip6 can act as a coactivator for the v-Rel transcription factor. 1079 23

An Arabidopsis protein was found to interact specifically with the capsid protein (CP) of turnip crinkle virus (TCV) through yeast two-hybrid screening. This protein, designated TIP (for TCV-interacting protein), was found to be a member of the recently recognized NAC family of proteins. NAC proteins have been implicated in the regulation of development of plant embryos and flowers. TIP alone was able to activate expression of reporter genes in yeast if fused to a DNA binding domain, suggesting that it may be a transcriptional activator. The TIP binding region in the TCV CP has been mapped to the N-terminal 25 amino acids. Site-directed mutagenesis within this region revealed that loss of the TIP-CP interaction in the yeast two-hybrid assay correlated with loss of the ability of TCV to induce the hypersensitive response and resistance in the TCV-resistant Arabidopsis ecotype Dijon (Di-0 and its inbred line Di-17). These data suggest that TIP is an essential component in the TCV resistance response pathway.
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PMID:HRT gene function requires interaction between a NAC protein and viral capsid protein to confer resistance to turnip crinkle virus. 1104 86

Ski interacting protein (Skip) has been found to bind to the highly conserved region of Ski, which is required for its transforming activity. Ski is a unique oncoprotein that is involved in inducing both transformation and differentiation. At the molecular level, Ski has been shown to exhibit either co-activator or co-repressor activity depending on the cellular and promoter context. We were interested in further elucidating the biological implications of the Ski-Skip interaction. Here we have identified the SNW domain of Skip as the interaction region for Ski. This domain of Skip is highly conserved in all the Skip homologues identified from different species. Using a series of reporter plasmids, we show that Skip is a potent transcriptional activator of many different promoters, the activity of which was also mapped to the conserved core SNW domain of the protein. Addition of excess Ski further augmented the transcriptional activities of Skip, suggesting that one of the ways in which Ski brings about transformation is by binding and cooperating with the SNW domain of Skip in transcriptional activation.
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PMID:Ski interacts with the evolutionarily conserved SNW domain of Skip. 1152 15

The common plant regulatory factors (CPRFs) from parsley are transcription factors with a basic-leucine-zipper motif that bind to cis-regulatory elements frequently found in promoters of light-regulated genes. Proposed to function in concert with members of other transcription factor families, CPRFs regulate the transcriptional activity of many target genes. Here, we report that, in contrast to CPRF2, which operates as a transcriptional activator, CPRF1 functions as repressor in vivo. Two-hybrid screens using CPRF1 and CPRF2 as "baits" resulted in the isolation of four novel parsley proteins which interact with either CPRF1 or CPRF2 in vivo. Three of these factors represent new parsley bZIP factors, designated CPRF5-CPRF7, whereas the fourth, named CPRF1-interacting protein (CIP), shows no homology to any other known protein. CPRF5 and CIP specifically interact with CPRF1, whilst CPRF6 and CPRF7 exclusively form heterodimers with CPRF2. CPRF5, CPRF6 and CPRF7 are transcription factors that exhibit sequence-specific DNA-binding as well as transactivation abilities, whereas the function of CIP remains elusive. The newly isolated CPRFs and CIP are constitutively localized in the nucleus in parsley protoplasts. Furthermore, mRNA accumulation studies revealed that the expression of these novel bZIP genes and CIP is not altered by exposure to light. We discuss the possible roles of the newly identified proteins in CPRF1- and CPRF2-dependent target gene expression.
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PMID:Isolation and characterization of four novel parsley proteins that interact with the transcriptional regulators CPRF1 and CPRF2. 1152 88

Beta-catenin is a key mediator of the Wnt pathway, which plays a critical role in embryogenesis and oncogenesis. As a transcriptional activator, beta-catenin binds the transcription factors, T-cell factor and lymphoid enhancer factor, and regulates gene expression in response to Wnt signaling. Abnormal activation of beta-catenin has been linked to various types of cancer. In a yeast two-hybrid screen, we identified the four and a half of LIM-only protein 2 (FHL2) as a novel beta-catenin-interacting protein. Here we show specific interaction of FHL2 with beta-catenin, which requires the intact structure of FHL2 and armadillo repeats 1-9 of beta-catenin. FHL2 cooperated with beta-catenin to activate T-cell factor/lymphoid enhancer factor-dependent transcription from a synthetic reporter and the cyclin D1 and interleukin-8 promoters in kidney and colon cell lines. In contrast, coexpression of beta-catenin and FHL2 had no synergistic effect on androgen receptor-mediated transcription, whereas each of these two coactivators independently stimulated AR transcriptional activity. Thus, the ability of FHL2 to stimulate the trans-activating function of beta-catenin might be dependent on the promoter context. The detection of increased FHL2 expression in hepatoblastoma, a liver tumor harboring frequent beta-catenin mutations, suggests that FHL2 might enforce beta-catenin transactivation activity in cancer cells. These findings reveal a new function of the LIM coactivator FHL2 in transcriptional activation of Wnt-responsive genes.
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PMID:Identification of the LIM protein FHL2 as a coactivator of beta-catenin. 1246 81

We previously identified a RING-IBR protein, RBCK1, as a protein kinase C (PKC) beta- and zeta-interacting protein, and its splice variant, RBCK2, lacking the C-terminal half including the RING-IBR domain. RBCK1 has been shown to function as a transcriptional activator whose nuclear translocation is prevented by interaction with the cytoplasmic RBCK2. We here demonstrate that RBCK1, like many other RING proteins, also possesses a ubiquitin ligase (E3) activity and that its E3 activity is inhibited by interaction with RBCK2. Moreover, RBCK1 has been found to undergo efficient phosphorylation by PKCbeta. The phosphorylated RBCK1 shows no self-ubiquitination activity in vitro. Overexpression of PKCbeta leads to significant increases in the amounts of intracellular RBCK1, presumably suppressing the proteasomal degradation of RBCK1 through self-ubiquitination, whereas coexpression with PKCalpha, PKCepsilon, and PKCzeta shows no or little effect on the intracellular amount of RBCK1. Taken together, the E3 activity of RBCK1 is controlled by two distinct manners, interaction with RBCK2 and phosphorylation by PKCbeta. It is possible that other RING proteins, such as Parkin, BRCA1, and RNF8, having the E3 activity, are also down-regulated by interaction with their RING-lacking splice variants and/or phosphorylation by protein kinases.
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PMID:Identification of ubiquitin ligase activity of RBCK1 and its inhibition by splice variant RBCK2 and protein kinase Cbeta. 1830 26

The peripheral nervous system is required for animals to detect and to relay environmental stimuli to central nervous system for the information processing. In Drosophila, the precise spatial and temporal expression of two proneural genes achaete (ac) and scute (sc), is necessary for development of the sensory organs. Here we present an evidence that the transcription co-repressor, dCtBP acts as a negative regulator of sensory organ prepattern. Loss of dCtBP function mutant exhibits ectopic sensory organs, while overexpression of dCtBP results in a dramatic loss of sensory organs. These phenotypes are correlated with mis-emerging of sensory organ precursors and perturbated expression of proneural transcription activator Ac. Mammalian CtBP-1 was identified via interaction with the consensus motif PXDLSX(K/R) of adenovirus E1A oncoprotein. We demonstrated that dCtBP binds directly to PLDLS motif of Drosophila Friend of GATA-1 protein, U-shaped and sharpens the adult sensory organ development. Moreover, we found that dCtBP mediates multivalent interaction with the GATA transcriptional activator Pannier and acts as a direct co-repressor of the Pannier-mediated activation of proneural genes. We demonstrated that Pannier genetically interacts with dCtBP-interacting protein HDAC1, suggesting that the dCtBP-dependent regulation of Pannier activity could utilize a repressive mechanism involving alteration of local chromatine structure.
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PMID:Drosophila C-terminal binding protein, dCtBP is required for sensory organ prepattern and sharpens proneural transcriptional activity of the GATA factor Pnr. 1877 87

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

In low GC content gram-positive bacteria, the HPr protein is the master regulator of carbon metabolism. HPr is a key component of the phosphoenolpyruvate (PEP):sugar phosphotransferase system that interacts with and/or phosphorylates proteins relevant to carbon catabolite repression. HPr can be phosphorylated by two distinct kinases as follows: the bifunctional enzyme HPr kinase/Ser(P)-HPr phosphorylase (HprK/P) phosphorylating the serine 46 residue (Ser(P)-HPr) and acting as a phosphorylase on Ser(P)-HPr; and the PEP-requiring enzyme I (EI) generating histidine 15-phosphorylated HPr (His(P)-HPr). The various HPr forms interact with numerous enzymes and modulate their activity. By carrying out a genome-wide yeast two-hybrid screen of a Bacillus subtilis library, we identified a novel HPr-interacting protein, the transcriptional activator YesS, which regulates the expression of pectin/rhamnogalacturonan utilization genes. Remarkably, yeast tri-hybrid assays involving the ATP-dependent HprK/P and the PEP-dependent EI suggested that YesS interacts with HPr and His(P)-HPr but not with Ser(P)-HPr. These findings were confirmed by in vitro interaction assays using the purified HPr-binding domain of the YesS protein. Furthermore, pectin utilization and in vivo YesS-mediated transcriptional activation depended upon the presence of His(P)-HPr, indicating that HPr-mediated YesS regulation serves as a novel type of carbon catabolite repression. In the yeast two-hybrid assays, B. subtilis HprK/P and EI were active and specifically recognized their substrates. Both kinases formed long lived complexes only with the corresponding nonphosphorylatable mutant HPr. These findings suggest that two-hybrid assays can be used for the identification of unknown kinases of phosphorylated bacterial proteins detected in phosphoproteome analyses.
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PMID:Transcriptional activator YesS is stimulated by histidine-phosphorylated HPr of the Bacillus subtilis phosphotransferase system. 1965 70


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