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)

A number of molecules have recently been described that effect the correct transport and assembly of cytoplasmically synthesized proteins to cellular membranes. To identify proteins that bind or modify other proteins during the process of membrane translocation, we developed a yeast selection scheme that employs the yeast transcriptional activator GAL4. This selection facilitates the isolation of cDNAs that encode proteases and binding proteins for known target peptide sequences. We report the isolation of an Arabidopsis cDNA encoding a polypeptide that can interact with the amino terminus of a ligh-harvesting chlorophyll a/b-binding protein (LHCP), a cytoplasmically synthesized protein that is integral to the chloroplast thylakoid membrane. The cDNA was selected in yeast from an Arabidopsis expression library for its ability to inhibit a transcriptional activator GAL4-LHCP fusion protein, but not inhibit native GAL4 protein. The LHCP amino-terminal sequences included in the fusion protein are known to regulate LHCP biogenesis and function. The Arabidopsis cDNA encodes a 595-amino acid protein with at least two functional domains, one with similarity to the family of protein-serine/threonine kinases and another that contains an epidermal growth factor repeat. The identification of an EGF repeat in Arabidopsis indicates that the motif is conserved between the plant and animal kingdoms. Hybridization studies indicate that this gene is likely to be present in other genera of plants. Its mRNA is detected in green leaves but not in other plant tissues or in etiolated plants. The specificity in yeast and the expression pattern in plants together are suggestive of a role for this protein kinase in the assembly or regulation of LHCP.
 ...
PMID:An Arabidopsis serine/threonine kinase homologue with an epidermal growth factor repeat selected in yeast for its specificity for a thylakoid membrane protein. 143 3

Recent efforts have been directed at identifying and characterizing candidate tumor suppressor genes and the activities of oncogenes in primary brain tumors. The p53 gene mapping to region p13 of chromosome 17 has several characteristics as a tumor suppressor gene. The wild-type p53 protein, which is a transcriptional activator, may serve as a barrier to the progression of neoplastic processes, and alterations of p53 are involved in genesis of various cancers including astrocytomas. The NF1 gene, which is responsible for the susceptibility to neurofibromatosis type 1, has recently been isolated. This gene is assumed to play a role in the signal transduction pathway by interacting with the ras gene product. Recent observation revealed that the NF1 gene may regulate the neuronal differentiation, and the alteration in regulation of the NF1 transcript is potentially related to the progression of neuroectodermal tumors. Restriction fragment length polymorphism studies have also shown chromosomal losses associated with chromosome 9, 10 and 17. These losses of genetic material are suspected to involve loci near or at the p53 gene for chromosome 17, and neighboring the interferon genes on chromosome 9. Although no sublocalization of chromosome 10 deletions has been accomplished, all of these loci are thought to harbor tumor suppressor genes. Recent advances in oncogene research have focused on understanding the mechanisms of action of growth factors, growth factor receptors, and their substrates, particularly in glial oncogenesis. Fibroblast growth factor, epidermal growth factor, and their respective receptors are of particular interest. However, the ROS oncogene, which is expressed and rearranged in some glioma cell lines, may not be a critical factor in the development of gliomas.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Pathways of oncogenesis in primary brain tumors. 190

Transforming growth factor-beta (TGF-beta) is a potent modulator of cell growth in many systems. In normal rat kidney (NRK) fibroblasts, TGF-beta synergizes with epidermal growth factor (EGF) to stimulate growth in soft agar, a characteristic of the transformed phenotype. Many biochemical effects of TGF-beta occur at the cell surface. Increased binding of EGF and synthesis of extracellular matrix components such as fibronectin and collagen are primary responses of NRK cells to TGF-beta. Although specific membrane receptors for TGF-beta have been identified, the mechanism of action of this factor is not well understood. Here we demonstrate that TGF-beta enhances the expression of the EGF receptor in NRK cells through an increase in the level of EGF receptor gene transcripts. Analysis of nuclear run-off transcription levels and mRNA half-lives indicate that the elevation in EGF-receptor mRNA results from an increase in the rate of transcription. Dose-response and kinetic studies suggest that the EGF receptor response to TGF-beta is biphasic, possibly resulting from the action of multiple TGF-beta receptors. TGF-beta also elevates the levels of fibronectin and tubulin transcripts in NRK cells; however, the mechanism differs for each gene. The increase in fibronectin mRNA in response to TGF-beta results from an increased rate of gene transcription. Tubulin mRNA levels, in contrast, appear to be post-transcriptionally regulated. These results implicate TGF-beta as a transcriptional activator of the genes for both the EGF receptor and fibronectin and suggest the two genes may be regulated through a common pathway in this cell type.
 ...
PMID:Transforming growth factor-beta increases transcription of the genes encoding the epidermal growth factor receptor and fibronectin in normal rat kidney fibroblasts. 319 40

Pituitary tumor-transforming gene (PTTG) is a recently characterized oncogene that can act as a transcriptional activator. In this study, we have characterized the transactivation domain of PTTG. Transient transfection of fusion constructs containing GAL4 DNA-binding domain and different parts of PTTG indicated the transactivation domain of PTTG is located between amino acids 119 and 164. Mitogen-activated protein (MAP) kinase cascade is important in the regulation of cell growth, apoptosis, and differentiation. Therefore, we have explored the possibility that this kinase cascade plays a role in regulating PTTG transactivation function. Activation of the MAP kinase cascade by epidermal growth factor or an expression vector for a constitutively active form of the MAP kinase kinase (MEK1) led to stimulation of PTTG transactivation activity. We showed that PTTG is phosphorylated in vitro on Ser(162) by MAP kinase and that this phosphorylation site plays an essential role in PTTG transactivation function. We demonstrated that PTTG interacts directly with MEK1 through a putative SH3 domain-binding site located between amino acids 51 and 54 and that this interaction is crucial for PTTG transactivation function. In addition, we showed that activation of MAP kinase phosphorylation cascade resulted in nuclear translocation of PTTG. Together, our data establish that a growth factor-stimulated MAP kinase plays an important role in modulating PTTG function.
 ...
PMID:Activation of mitogen-activated protein kinase cascade regulates pituitary tumor-transforming gene transactivation function. 1090 23

Notch is a single-pass transmembrane receptor that mediates cell fate choice in various species and developmental contexts. The Notch signal is transduced by its intracellular domain, which acts as a transcriptional activator, and is released from the plasma membrane by proteolytic cleavages. This process is initiated by intercellular association of the epidermal growth factor (EGF) repeats between Notch and the DSL (Delta, Serrate, Lag-2) ligands but the detailed mechanism is yet to be clarified. Here we demonstrate that Notch1 can form homodimers, which is achieved by its EGF motifs. The Notch1 dimer formation increased in response to ligand presentation and HES1 promoter was stimulated, implying that receptor homodimerization is an important initial step in Notch signal transduction. EGF motifs also serve as a protection against proteases, including TNF-alpha converting enzyme, which prevents Notch1 from ligand-independent activation. Multiple functions of the Notch EGF motifs, such as the prevention of constitutive activation, reciprocal interaction with the ligands and lateral interaction for homodimerization, appear to constitute crucial elements of the Notch signaling system.
 ...
PMID:Distinct roles of EGF repeats for the Notch signaling system. 1556 Nov 8