Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

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

Mirk/Dyrk1B protein kinase was shown in an earlier study to function as a transcriptional activator of HNF1alpha, which Mirk phosphorylates at Ser(249) within its CREB (cAMP-response element-binding protein)-binding protein (CBP) binding domain (). The MAPK kinase MKK3 was also shown to activate Mirk as a protein kinase, implicating Mirk in the biological response to certain stress agents. Another MKK3 substrate, p38MAPK, is now shown to inhibit the function of Mirk as a transcriptional activator in a kinase-independent manner. Co-immunoprecipitation experiments demonstrated that kinase-inactive p38AF, as well as wild-type p38, sequestered Mirk and prevented its association with MKK3. Only the p38alpha and p38beta isoforms, but not the gamma or delta isoforms, complexed with Mirk. p38alphaMAPK blocked Mirk activation of HNF1alpha in a dose-dependent manner, with high levels of kinase-inactive p38alphaAF completely suppressing the activity of Mirk. Size fractionation by fast protein liquid chromatography on Superdex 200 demonstrated that Mirk is not found as a monomer in vivo, but is found within 150-700 kDa subnuclear complexes, which co-migrate with the nuclear body scaffolding protein PML. Endogenous Mirk, p38, and MKK3 co-migrate within 500-700-kDa protein complexes, which accumulate when nuclear export is blocked by leptomycin B. Stable overexpression of Mirk increases the fraction of Mirk protein and p38 protein within these 500-700 kDa complexes, suggesting that the complexes act as nuclear depots for Mirk and p38. Sequestration of Mirk by p38 may occur within these subnuclear complexes. Synchronization experiments demonstrated that Mirk levels fluctuate about 10-fold within the cell cycle, while p38 levels do not, leading to the speculation that endogenous p38 could only block Mirk function when Mirk levels were low in S phase and not when Mirk levels were elevated in G(0)/G(1). These data suggest a novel cell cycle-dependent function for p38, suppression of the function of Mirk as a transcriptional activator only when cells are proliferating, and thus limiting Mirk function to growth-arrested cells.
...
PMID:The transcriptional activator Mirk/Dyrk1B is sequestered by p38alpha/beta MAP kinase. 1238 4

The human T-cell leukemia virus (HTLV-I)-encoded Tax protein is a potent transcriptional activator that stimulates expression of the integrated provirus. Biochemical studies indicate that Tax, together with cellular transcription factors, interacts with viral cAMP-response element enhancer elements to recruit the pleiotropic coactivators CREB-binding protein and p300. Histone acetylation by these coactivators has been shown to play a major role in activating HTLV-I transcription from chromatin templates in vitro. However, the extent of histone modification and the precise identity of the cellular regulatory proteins bound at the HTLV-I promoter in vivo is not known. Chromatin immunoprecipitation analysis was used to investigate factor binding and histone modification at the integrated HTLV-I provirus in infected T-cells (SLB-1). These studies reveal the presence of Tax, a variety of ATF/CREB and AP-1 family members (CREB, CREB-2, ATF-1, ATF-2, c-Fos, and c-Jun), and both p300 and CREB-binding protein at the HTLV-I promoter. Consistent with the binding of these coactivators, we observed histone H3 and H4 acetylation at three regions within the proviral genome. Histone deacetylases were also present at the viral promoter and, following their inhibition, we observe an increase in histone H4 acetylation on the HTLV-I promoter and a concomitant increase in viral RNA. Together, these results suggest that a variety of transcriptional activators, coactivators, and histone deacetylases participate in the regulation of HTLV-I transcription in infected T-cells.
...
PMID:Transcription factor binding and histone modifications on the integrated proviral promoter in human T-cell leukemia virus-I-infected T-cells. 1238 57

The cAMP responsive transcriptional factor, CREB, is highly conserved among animal species, and its activity affects their behavior. In Drosophila melanogaster, one of alternatively spliced products of the CREB gene, dCREB2-a, is a transcriptional activator, while another isoform, dCREB2-b, is a repressor of dCREB2-a. Here, we demonstrate that overexpression of dCREB2-b in virgin females enhances their sexual receptivity. We studied the role of dCREB2 in female mating behavior using two transgenic lines, hs-dCREB2-a and hs-dCREB2-b, which overexpress respective products with heat-shock treatment. Wild-type males started their courtship behavior and mated more quickly with heat-shocked hs-dCREB2-b females than with non-heat-shocked hs-dCREB2-b females. Overexpression of dCREB2-a in females affected neither their courtship behavior nor mating frequency. The effects of overexpressed dCREB2-b were not due to elevated locomotor activities of heat-shocked females nor due to more vigorous courtship behavior of paired wild-type males. CREB might be involved in female sexual behavior of animals.
...
PMID:Overexpression of a CREB repressor isoform enhances the female sexual receptivity in Drosophila. 1246 39

The HIV-1 transactivator protein, Tat, is an atypical transcriptional activator that functions through binding, not to DNA, but to a short leader RNA, TAR. Although details of its functional mechanism are still unknown, emerging findings suggest that Tat serves primarily to adapt co-activator complexes such as p300, PCAF and P-TEFb to the HIV-1 long terminal repeat. Hence, an understanding of how Tat interacts with these cofactors is crucial. It has recently been shown that acetylation at a single lysine, residue 50, regulated the association of Tat with PCAF. Here, we report that in the absence of Tat acetylation, PCAF binds to amino acids 20-40 within Tat. Interestingly, acetylation of Tat at Lys28 abrogates Tat-PCAF interaction. Acetylation at Lys50 creates a new site for binding to PCAF and dictates the formation of a ternary complex of Tat-PCAF-P-TEFb. Thus, differential lysine acetylation of Tat coordinates the interactions with its co-activators, cyclin T1 and PCAF. Our results may help in understanding the ordered recruitment of Tat co-activators to the HIV-1 promoter.
...
PMID:Differential acetylation of Tat coordinates its interaction with the co-activators cyclin T1 and PCAF. 1248 2

Dimerization is a widely believed critical requirement for the yeast transcriptional activator GCN4 specifically recognizing its DNA target sites. Nonetheless, the binding of the monomeric GCN4 to DNA target sites AP-1 and ATF/CREB was recently detected by kinetic studies. Here, for the first time, we present a detailed description of the thermodynamics of a monomeric peptide GCN4-br, the basic region (226-252) of GCN4, binding to AP-1, and ATF/CREB. GCN4 specifically binds to AP-1 and ATF/CREB in the monomeric form as shown by our circular dichroism thermal unfolding measurements. Isothermal titration calorimetry experiments indicate that the binding process of GCN4-br with DNA is enthalpically driven, accompanied by an unfavorable entropy change. The temperature dependence of DeltaH(0) reveals negative changes in heat capacity DeltaC(p): DeltaC(p) = -0.92 kJ. mol(-1) K(-1) and DeltaC(p) = -0.95 kJ. mol(-1) K(-1) for GCN4-br binding to AP-1 and ATF/CREB, respectively, which is a striking manifestation of GCN4-br specifically recognizing DNA target sites. These thermodynamic characteristics may give new insight into the mechanism by which GCN4 protein binds to DNA target sites for its transcriptional regulation.
...
PMID:Thermodynamic characterization of the folding coupled DNA binding by the monomeric transcription activator GCN4 peptide. 1260 88

The SNF2-related CBP activator protein (SrCap) is a potent activator of transcription mediated by CBP and CREB. We have previously demonstrated that the Adenovirus 2 DNA Binding Protein (DBP) binds to SrCap and inhibits the transcription mediated by the carboxyl-terminal region of SrCap (amino acids 1275-2971). We report here that DBP inhibits the ability of full-length SrCap (1-2971) to activate transcription mediated by Gal-CREB and Gal-CBP. In addition, DBP also inhibits the ability of SrCap to enhance Protein Kinase A (PKA) activated transcription of the enkaphalin promoter. DBP was found to dramatically inhibit transcription of a mammalian two-hybrid system that was dependent on the interaction of SrCap and CBP binding domains. We also found that DBP has no effect on transcription mediated by a transcriptional activator that is not related to SrCap, indicating that our reported transcriptional inhibition is specific for SrCap and not due to nonspecific effects of DBP's DNA binding activity on the CAT reporter plasmid. Taken together, these results suggest a model in which DBP inhibits cellular transcription mediated by the interaction between SrCap and CBP.
...
PMID:Adenovirus DNA binding protein inhibits SrCap-activated CBP and CREB-mediated transcription. 1295 26

The HTLV-1 transcriptional activator Tax is required for viral replication and pathogenesis. In concert with human CREB, Tax recruits the human transcriptional coactivator and histone acetyltransferase p300/CBP to the HTLV-1 promoter. Here we investigate the structural features of the interaction between Tax and the KIX domain of p300/CBP. Circular dichroism spectroscopy, nuclear magnetic resonance chemical shift perturbation mapping, and sedimentation equilibrium analysis show that KIX binds a Tax subdomain corresponding to residues 59-98 of Tax (called Tax(59-98)). Circular dichroism spectroscopy suggests that Tax(59-98) is intrinsically disordered (natively unfolded) in isolation and adopts an ordered conformation upon binding KIX. The interaction is disrupted by a single amino acid variation of Tax(59-98) in which leucine 68 is substituted with proline. Chemical shift perturbation mapping reveals that the Tax-binding surface of KIX is distinct from that utilized by CREB, and corresponds to the site of KIX that interacts with the human transcription factors c-Jun and mixed lineage leukemia protein (MLL). Sedimentation equilibrium analysis shows that Tax and the phosphorylated KID domain of CREB can simultaneously bind KIX to form a ternary 1:1:1 complex. The results provide a molecular description of the concerted recruitment of p300/CBP via the KIX domain by Tax and phosphorylated CREB during Tax-mediated gene expression.
...
PMID:KIX-mediated assembly of the CBP-CREB-HTLV-1 tax coactivator-activator complex. 1458 Jan 93

In response to environmental stress, cells induce a program of gene expression designed to remedy cellular damage or, alternatively, induce apoptosis. In this report, we explore the role of a family of protein kinases that phosphorylate eukaryotic initiation factor 2 (eIF2) in coordinating stress gene responses. We find that expression of activating transcription factor 3 (ATF3), a member of the ATF/CREB subfamily of basic-region leucine zipper (bZIP) proteins, is induced in response to endoplasmic reticulum (ER) stress or amino acid starvation by a mechanism requiring eIF2 kinases PEK (Perk or EIF2AK3) and GCN2 (EIF2AK4), respectively. Increased expression of ATF3 protein occurs early in response to stress by a mechanism requiring the related bZIP transcriptional regulator ATF4. ATF3 contributes to induction of the CHOP transcriptional factor in response to amino acid starvation, and loss of ATF3 function significantly lowers stress-induced expression of GADD34, an eIF2 protein phosphatase regulatory subunit implicated in feedback control of the eIF2 kinase stress response. Overexpression of ATF3 in mouse embryo fibroblasts partially bypasses the requirement for PEK for induction of GADD34 in response to ER stress, further supporting the idea that ATF3 functions directly or indirectly as a transcriptional activator of genes targeted by the eIF2 kinase stress pathway. These results indicate that ATF3 has an integral role in the coordinate gene expression induced by eIF2 kinases. Given that ATF3 is induced by a very large number of environmental insults, this study supports involvement of eIF2 kinases in the coordination of gene expression in response to a more diverse set of stress conditions than previously proposed.
...
PMID:Activating transcription factor 3 is integral to the eukaryotic initiation factor 2 kinase stress response. 1472 79

Expression of human T-cell leukemia virus type 1 (HTLV-1) is regulated by the viral transcriptional activator Tax. Tax activates viral transcription through interaction with the cellular transcription factor CREB and the coactivators CBP/p300. In this study, we have analyzed the role of histone deacetylase 1 (HDAC1) on HTLV-1 gene expression from an integrated template. First we show that trichostatin A, an HDAC inhibitor, enhances Tax expression in HTLV-1-transformed cells. Second, using a cell line containing a single-copy HTLV-1 long terminal repeat, we demonstrate that overexpression of HDAC1 represses Tax transactivation. Furthermore, a chromatin immunoprecipitation assay allowed us to analyze the interaction of transcription factors, coactivators, and HDACs with the basal and activated HTLV-1 promoter. We demonstrate that HDAC1 is associated with the inactive, but not the Tax-transactivated, HTLV-1 promoter. In vitro and in vivo glutathione S-transferase-Tax pull-down and coimmunoprecipitation experiments demonstrated that there is a direct physical association between Tax and HDAC1. Importantly, biotinylated chromatin pull-down assays demonstrated that Tax inhibits and/or dissociates the binding of HDAC1 to the HTLV-1 promoter. Our results provide evidence that Tax interacts directly with HDAC1 and regulates binding of the repressor to the HTLV-1 promoter.
...
PMID:Tax relieves transcriptional repression by promoting histone deacetylase 1 release from the human T-cell leukemia virus type 1 long terminal repeat. 1519 48

Despite the small size of its genome (3.2 kb) and having only four genes that are encoded within it, the hepatitis B virus (HBV) is one of the most successful viral pathogens in human history. It is estimated that there are about 350-400 million people worldwide who are chronically infected with HBV, and even with the extensive efforts that are being done with preventive vaccination, this malady still remains a clear and present danger to the public health. How is it possible that this small double-stranded DNA virus can escape and outfox the surveillance of the complex human immune system? One explanation is that HBV gene products play multiple roles in infections and throughout the viral life cycle so that the virus can effectively survive under various hostile circumstances. Indeed, the HBV DNA polymerase, for example, exerts several functions such as reverse transcription and RNA degradation, and the HBV X protein not only acts as a transcriptional activator, but it also interferes with the host cells' DNA repair mechanism as well as inducing apoptosis and controlling signal transduction. The HBV surface protein, which is encoded in the env gene, is another intriguing example of such multifunctionality. Thus, our present article overviews and summarizes the multifaceted role of this membrane protein as shown in 1) its role as a structural protein of the virus envelope; 2) its function as the viral ligand for interacting with the viral receptors on host cells; 3) its characteristics as an energy-independent transporter molecule that can mediate the nuclear accumulation of itself and other tagged molecules; 4) its role as a viral transactivator protein that can cause hepatocellular carcinoma; 5) its hypothetical function in viral apoptotic mimicry that results in host anti-inflammatory responses; and last 6) its immunostimulatory property by providing for strong and well-defined B- and T-cell epitopes. Understanding these various functions and the versatility of this single protein will help us decipher and understand the viral- and immuno-pathogenesis of HBV itself.
...
PMID:[Hepatitis B virus surface antigen: a multifaceted protein]. 1561


<< Previous 1 2 3 4 5 6 7 Next >>

---