Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In human cells infected with herpes simplex virus (HSV), viral gene expression is initiated by the virion protein VP16. VP16 does not bind DNA directly but forms a multiprotein complex on the viral immediate-early gene promoters with two cellular proteins: the POU domain protein Oct-1 and host cell factor (HCF; also called C1, VCAF, and CFF). Despite its apparent role in stabilizing the VP16-induced transcription complex, the natural biological role of HCF is unclear. Only recently HCF has been implicated in control of the cell cycle. To determine the role of HCF in cells and answer why HSV has evolved an HCF-dependent mechanism for the initiation of the lytic cycle, we identified the first human ligand for HCF (R. Lu et al., Mol. Cell. Biol. 17:5117-5126, 1997). This protein, Luman, is a member of the CREB/ATF family of transcription factors that can activate transcription from promoters containing cyclic AMP response elements (CRE). Here we provide evidence that Luman and VP16 share two important structural features: an acidic activation domain and a common mechanism for binding HCF. We found that Luman, its homolog in Drosophila, dCREB-A (also known as BBF-2), and VP16 bind to HCF by a motif, (D/E)HXY(S/A), present in all three proteins. In addition, a mutation (P134S) in HCF that prevents VP16 binding also abolishes its binding to Luman and dCREB-A. We also show that while interaction with HCF is not required for the ability of Luman to activate transcription when tethered to the GAL4 promoter, it appears to be essential for Luman to activate transcription through CRE sites. These data suggest that the HCF-Luman interaction may represent a conserved mechanism for transcriptional regulation in metazoans, and HSV mimics this interaction with HCF to monitor the physiological state of the host cell.
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PMID:The herpesvirus transactivator VP16 mimics a human basic domain leucine zipper protein, luman, in its interaction with HCF. 965 67

Activated T cells have been implicated in chronic rhinosinusitis (CRS) and asthma and physically interact with epithelial cells in the airways. We now report that human airway epithelial cells display significant constitutive cell-surface expression of costimulatory ligands, B7-H1, B7-H2, B7-H3, and B7-DC. Expression of B7-H1 and B7-DC was selectively induced by stimulation of either BEAS2B or primary nasal epithelial cells (PNEC) with interferon (IFN)-gamma (100 ng/ml). The combination of IFN-gamma and tumor necrosis factor-alpha (100 ng/ml) selectively induced expression better than IFN-gamma alone. Fluticasone treatment (10(-7) M) reduced the baseline expression and inhibited the induction of B7-H1 and B7-DC in BEAS2B cells. In vitro exposure of PNEC to IFN-gamma also resulted in selective induction of B7-H1 and B7-DC. Monoclonal antibody blockade of B7-H1 or B7-DC enhanced IFN-gamma expression by purified T cells in co-culture experiments, suggesting that these two B7 homologs inhibit T cell responses at the mucosal surface. Immunohistochemical staining of human sinonasal surgical tissue confirmed the presence of B7-H1, B7-H2, and B7-H3 in the epithelial cell layer, especially in samples from patients diagnosed with Samter's Triad, a severe form of CRS. Real-time PCR analysis of sinonasal tissue revealed elevated levels of B7-H1 and B7-DC in CRS compared with controls. These results demonstrate that epithelial cells express functional B7 costimulatory molecules and that expression of selected B7 family members is inducible in vitro and in vivo. Epithelial B7 homologs could play a role in regulation of lymphocytic activity at mucosal surfaces.
Am J Respir Cell Mol Biol 2005 Sep
PMID:Constitutive and inducible expression of b7 family of ligands by human airway epithelial cells. 1596 27

A molecular tweezer, zinc porphyrin-dithienylethene-zinc porphyrin (ZnP-DTE-ZnP) triad, has been prepared. Triad ZnPor-DTE-ZnPor showed a little electronic communication among the chromophores judged from the comparison of the steady-state absorption and fluorescence spectra for triads and their component compounds. Irradiation of ZnPor-DTE-ZnPor with UV light converts dithienylethene moiety from open form to closed form. The complexation of ZnP-DTE-ZnP with 4,4'-bipyridyl were investigated by absorption and fluorescence spectroscopic measurements. ZnP-DTE-ZnP forms a 1:1 complex with 4,4'-bipyridyl. The stability constants of log K=4.0 and 4.2 mol(-1)dm3 were determined by absorption and fluorescence spectral changes, respectively.
Spectrochim Acta A Mol Biomol Spectrosc 2007 Nov
PMID:Molecular tweezer based on zinc porphyrin-substituted diarylethene. 1732 55

Human papillomavirus (HPV) is considered to be a major etiological factor but is not sufficient for the development of cervical cancer. Other host factors including altered tumor suppressor gene activities might contribute to the carcinogenic process. Fragile Histidine Triad (FHIT) has been shown to play a pivotal role in carcinogenesis. Therefore, we made an attempt to find out point mutation of FHIT gene in HPV mediated cervical cancer in Indian women. 112 cases of cervical carcinoma tissue biopsies and 38 cervical scrapes samples of normal cytology were employed for this study. Herein, we report a novel mutation identified at nucleotide position 655, at codon 98 from CAT --> CGT with ultimate replacement of amino acid Histidine by Arginine in cervical cancer cases. Molecular modeling was performed to predict the effect of this mutation in disease pathology. We predict that this change, His to Arg substitution in substrate-binding domain may generate catalytically inactive protein with loss of tumor suppressor activity.
Mol Cell Biochem 2010 Feb
PMID:Novel missense mutation in FHIT gene: interpreting the effect in HPV-mediated cervical cancer in Indian women. 1973 Sep 90

The CFTR Folding Consortium (CFC) was formed in 2004 under the auspices of the Cystic Fibrosis Foundation and its drug discovery and development affiliate, CFF Therapeutics. A primary goal of the CFC is the development and distribution of reagents and assay methods designed to better understand the mechanistic basis of mutant CFTR misfolding and to identify targets whose manipulation may correct CFTR folding defects. As such, reagents available from the CFC primarily target wild-type CFTR NBD1 and its common variant, F508del, and they include antibodies, cell lines, constructs, and proteins. These reagents are summarized here, and two protocols are described for the detection of cell surface CFTR: (a) an assay of the density of expressed HA-tagged CFTR by ELISA and (b) the generation and use of an antibody to CFTR's first extracellular loop for the detection of endogenous CFTR. Finally, we highlight a systematic collection of assays, the CFC Roadmap, which is being used to assess the cellular locus and mechanism of mutant CFTR correction. The Roadmap queries CFTR structure-function relations at levels ranging from purified protein to well-differentiated human airway primary cultures.
Methods Mol Biol 2011
PMID:CFTR Folding Consortium: methods available for studies of CFTR folding and correction. 2154 42