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)

Infection of human epidermoid carcinoma No. 2 cells with herpes simplex virus type 1 (HSV-1) leads to a reorganization of antigens associated with both the small and heterogeneous nuclear ribonucleoprotein complexes (snRNP and hnRNP). The hnRNP core protein antigens remain associated with the host chromatin, which appears to collapse into internal aggregates and along the nuclear envelope. More striking is the formation of prominent clusters of snRNP antigens (both general and U1 snRNP specific), which appear to condense throughout the nucleus then migrate to the periphery. These snRNP clusters have been identified at the fine structure level by immuno-electron microscopy. The HSV-1 presumed transcriptional activator ICP4, DNA-binding protein ICP8, and two capsid proteins ICP5 and p40 are not detectably associated with the snRNP clusters. Similar reorganization of snRNP occurs with HSV-2 and upon infection of African green monkey VERO cells with HSV-1. We speculate that the snRNP clusters arise from an increase in size and density of the interchromatin granule region of the host cell as a result of the partial inactivation of snRNP and host pre-mRNA splicing.
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PMID:Redistribution of nuclear ribonucleoprotein antigens during herpes simplex virus infection. 282 25

Enhancer-dependent transcriptional activators that act upon the sigma54 bacterial RNA polymerase holoenzyme belong to the extensive AAA+ superfamily of mechanochemical ATPases. Formation and collapse of the transition state for ATP hydrolysis engenders direct interactions between AAA+ activators and the sigma54 factor, required for RNA polymerase isomerization. A DNA fork junction structure present within closed complexes serves as a nucleation point for the DNA melting seen in open promoter complexes and restricts spontaneous activator-independent RNA polymerase isomerization. We now provide physical evidence showing that the ADP.AlF(x) bound form of the AAA+ domain of the transcriptional activator protein PspF changes interactions between sigma54-RNA polymerase and a DNA fork junction structure present in the closed promoter complex. The results suggest that one functional state of the nucleotide-bound activator serves to alter DNA binding by sigma54 and sigma54-RNA polymerase and appears to drive events that precede DNA opening. Clear evidence for a DNA-interacting activity in the AAA+ domain of PspF was obtained, suggesting that PspF may make a direct contact to the DNA component of a basal promoter complex to promote changes in sigma54-RNA polymerase-DNA interactions that favour open complex formation. We also provide evidence for two distinct closed promoter complexes with differing stabilities.
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PMID:Nucleotide-dependent interactions between a fork junction-RNA polymerase complex and an AAA+ transcriptional activator protein. 1533 92

Hepatitis B virus (HBV) is a small hepatotropic and highly species-specific enveloped DNA virus. The carcinogenicity of this virus has become focused on the X gene and its coded X protein. The X protein itself is unable to bind to DNA directly, but works as a potent transcriptional activator through multiple cis-acting elements and mediates several signal transduction cascades. Two regions of the X protein, aa.61-69 and aa.105-140, are found essential for the viral replication and expression as well. These functions interacting with transcription factors and signaling cascades are acting cooperatively to cause cell proliferation. Furthermore, the association of X protein with mitochondria causes loss of the mitochondrial membrane potential and subsequently causes cell death, the function of which is attributed to the aa.68-104 region of X protein. As a result, the X protein has two independent proliferative and cell death-promoting activities. Liver cancer has been shown to result from a series of mutations in specific oncogenes and tumor suppressor genes. In a recent study, X protein stimulates ROS generation in the mitochondria due to collapse of the membrane potential and increases the mutation frequency, that evokes malignant transformation. Inflammation as a result of HBV infection is concerned to cause DNA damage. In the past 10years, the possibility that several viral proteins directly engaged in the DNA damage has increased to some extent. From an evolutionary viewpoint, it is noteworthy that several arrangement proteins have been found in viruses. Thus, there is some clue that a small amount of X protein acts as an arrangement protein for HBV replication dependent upon cellular DNA damage due to generated ROS as an amplified signal.
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PMID:Hepatitis B virus X gene is implicated in liver carcinogenesis. 1946 4

Immune cells exploit reactive oxygen species (ROS) and cationic fluxes to kill microbial pathogens, such as the fungus Candida albicans. Yet, C. albicans is resistant to these stresses in vitro. Therefore, what accounts for the potent antifungal activity of neutrophils? We show that simultaneous exposure to oxidative and cationic stresses is much more potent than the individual stresses themselves and that this combinatorial stress kills C. albicans synergistically in vitro. We also show that the high fungicidal activity of human neutrophils is dependent on the combinatorial effects of the oxidative burst and cationic fluxes, as their pharmacological attenuation with apocynin or glibenclamide reduced phagocytic potency to a similar extent. The mechanistic basis for the extreme potency of combinatorial cationic plus oxidative stress--a phenomenon we term stress pathway interference--lies with the inhibition of hydrogen peroxide detoxification by the cations. In C. albicans this causes the intracellular accumulation of ROS, the inhibition of Cap1 (a transcriptional activator that normally drives the transcriptional response to oxidative stress), and altered readouts of the stress-activated protein kinase Hog1. This leads to a loss of oxidative and cationic stress transcriptional outputs, a precipitous collapse in stress adaptation, and cell death. This stress pathway interference can be suppressed by ectopic catalase (Cat1) expression, which inhibits the intracellular accumulation of ROS and the synergistic killing of C. albicans cells by combinatorial cationic plus oxidative stress. Stress pathway interference represents a powerful fungicidal mechanism employed by the host that suggests novel approaches to potentiate antifungal therapy. Importance: The immune system combats infection via phagocytic cells that recognize and kill pathogenic microbes. Human neutrophils combat Candida infections by killing this fungus with a potent mix of chemicals that includes reactive oxygen species (ROS) and cations. Yet, Candida albicans is relatively resistant to these stresses in vitro. We show that it is the combination of oxidative plus cationic stresses that kills yeasts so effectively, and we define the molecular mechanisms that underlie this potency. Cations inhibit catalase. This leads to the accumulation of intracellular ROS and inhibits the transcription factor Cap1, which is critical for the oxidative stress response in C. albicans. This triggers a dramatic collapse in fungal stress adaptation and cell death. Blocking either the oxidative burst or cationic fluxes in human neutrophils significantly reduces their ability to kill this fungal pathogen, indicating that combinatorial stress is pivotal to immune surveillance.
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PMID:Mechanisms underlying the exquisite sensitivity of Candida albicans to combinatorial cationic and oxidative stress that enhances the potent fungicidal activity of phagocytes. 2590 Jun 57