Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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The replication of many retroviruses is mediated by a transcriptional activator protein, Tat, which activates RNA polymerase II at the level of transcription elongation. Tat interacts with Cyclin T1 of the positive transcription-elongation factor P-TEFb to recruit the transactivation-response TAR RNA, which acts as a promoter element in the transcribed 5' end of the viral long terminal repeat. Here we present the structure of the cyclin box domain of Cyclin T1 in complex with the Tat protein from the equine infectious anemia virus and its corresponding TAR RNA. The basic RNA-recognition motif of Tat adopts a helical structure whose flanking regions interact with a cyclin T-specific loop in the first cyclin box repeat. Together, both proteins coordinate the stem-loop structure of TAR. Our findings show that Tat binds to a surface on Cyclin T1 similar to where recognition motifs from substrate and inhibitor peptides were previously found to interact within Cdk-cyclin pairs.
Nat Struct Mol Biol 2008 Dec
PMID:Structural insights into the cyclin T1-Tat-TAR RNA transcription activation complex from EIAV. 1902 97

Some transition metal complexes of the type [ML2].nH2O (n=0 or 2) of the title ligand, 4-(2-thiazolylazo)resorcinol, HL (TAR) have been synthesized and characterized by various analytical and physicochemical (elemental, thermal analyses, AAS, electrolytic conductance and magnetic susceptibility measurements) and spectral (UV-vis and IR) techniques for structure determination and optical properties. The complexes have the formulae [ML2] for M=Fe(II), Cu(II) and Zn(II); [CdL2].2H2O. An octahedral structure is proposed for all complexes. IR spectra show that the ligand is coordinated to the metal ions in a tridentate manner with ONN donor sites of the resorcinol OH, azo N and thiazole N. The effect of varying pH and solvent on the absorption behavior of the ligand and complexes has been investigated. The optical constants such as, refractive index, extinction coefficient, dielectric constant were determined for the ligand and its complexes. These parameters changed with different metal complexes. The optical absorption data revealed that the band gap of the films was direct transitions. The optical band gap and Urbach energy of the films were determined using the known theory. The optical dispersion parameters were determined according to Wemple and DiDomenico method.
Spectrochim Acta A Mol Biomol Spectrosc 2009 Jul
PMID:Synthesized some 4-(2-thiazolylazo)resorcinol complexes: characterization, thermal and optical properties. 1929 40

Tartrate-resistant acid phosphatase (TRAP) is highly expressed in osteoclasts and chondroclasts. The present study investigated changes in TRAP activity after chondrocyte death and cartilage damage, and also evaluated the possible use of TRAP as a diagnostic factor in a model of osteoarthritis. We induced experimental osteoarthritis in beagle dogs and separated chondrocytes from articular cartilage using an enzyme probe. Chondrocyte death was induced by proteasome inhibition and TRAIL treatment, and levels of lactate dehydrogenase, reactive oxygen species (ROS), caspase activation and TRAP activity were measured in the chondrocytes and synovial fluid. Proteasome inhibition and TRAIL treatment significantly enhanced chondrocyte death via caspase-8 activation and ROS generation in the primary cultured canine chondrocytes. TRAP activity was highly increased in damaged chondrocytes, but was decreased by blocking chondrocyte death using caspase inhibition or an ROS scavenger. In the synovial fluid of osteoarthritic dogs, TRAP activity as well as caspase activation and ROS levels were higher than those in the normal joint. Our study demonstrated that TRAP is activated by apoptosis and oxidative stress in primary cultured chondrocytes and osteoarthritic joints and also suggests that TRAP may be used as a diagnostic biomarker for detection of cartilage-related diseases, including osteoarthritis.
Int J Mol Med 2009 Jul
PMID:Tartrate-resistant acid phosphatase as a diagnostic factor for arthritis. 1951 35

An important problem in the development of gene therapy approaches in oncology is the necessity of using promoters providing specific and high level of gene expression in tumor cells. To solve this problem, we used inducible system of gene expression regulation (Tat-TAR-system), which is utilized by human immunodeficiency virus (HIV). tat and tk-HSV genes, as well as a fragment of LTR HIV-1, were cloned in the retrovirus vector, tk-HSV gene was under control of the LTR HIV-1 fragment. Potential capacity of these constructions for transactivating tk-HSV gene transcription was studied. Basal expression level of this gene was defined in transient transfection of HEK293 cells. It was shown that specific transactivation of the tk-HSV gene was controlled by the LTR HIV-1 fragment in lung carcinoma cells Calu-1, permanently transfected by the tat gene construction. The effect of transactivation of tk-HSV transcription in Tat-TAR-system was demonstrated in Calu-1 cells in conditions of control of cancer-specific tat gene over BIRC5 promoter.
Mol Gen Mikrobiol Virusol 2009
PMID:[Study of transactivation effect on transcription by Tat-TAR-system of human immunodeficiency virus type 1 (HIV-1) in non-lymphoid cells HEK293 and Calu-1]. 1951 4

The only specific marker of sporadic amyotrophic lateral sclerosis (ALS) is neuropathologic, namely the presence of inclusions staining positively for ubiquitin and TAR DNA-binding protein (TARDBP, also known as TDP-43) in degenerating motor neurons. Abnormalities in various physiopathologic pathways associated with ALS, such as oxidative stress, inflammation, and excitotoxicity, have been reported in blood, cerebrospinal fluid, and muscle biopsies. A number of studies in ALS patients have indicated that nuclear magnetic resonance (NMR) spectroscopy and diffusion tensor magnetic resonance imaging (MRI) can detect corticospinal lesions. However, because of their relative lack of sensitivity and specificity, these techniques are currently inadequate for use as diagnostic tools in individual patients. Recently, there has been much interest in the use of high-throughput techniques such as transcriptomics, proteomics, and metabolomics for the detection of biomarkers. In the future, a combination of biologic, radiologic, and electrophysiologic markers, rather than a single marker, may prove a useful tool for the diagnosis and follow-up of ALS patients. This article provides an overview of recently described biologic and radiologic markers of the disease.
Mol Diagn Ther 2009
PMID:Biomarkers in amyotrophic lateral sclerosis: facts and future horizons. 1953 46

The recognition that RNA is more than just an intermediate in the information transfer from genetic code to fully functional protein has placed it at the forefront of chemical research. RNA is important because of its vital role in regulating transcription, translation, splicing, replication and catalysis. Consequently, molecules that can bind to RNA and control its function have potential as powerful tools in biology and medicine. Herein, we report the discovery of HIV-1 TAR RNA-selective ligands using an on-bead screening of a library of 4096 branched peptides.
Mol Biosyst 2009 Sep
PMID:Screening of a branched peptide library with HIV-1 TAR RNA. 1966 73

Amyotrophic lateral sclerosis (ALS) is the most common adult motor neuron disease that affects approximately 2/100,000 individuals each year worldwide. Patients with ALS suffer from rapidly progressive degeneration of motor neurons ultimately leading to death. The major pathological features observed in post-mortem tissue from patients with ALS are motor neuron loss, cortical spinal tract degeneration, gliosis and cytoplasmic neuronal inclusions formed by TDP-43 or TAR DNA binding Protein with a molecular mass of 43 kDa, which are now recognized as the signature lesions of sporadic ALS. TDP-43 possesses two RNA binding domains (RBD) and a glycine-rich C terminus classifying it with other heterogeneous nuclear ribonucleoproteins known as 2XRBD-Gly proteins. A number of reports showed that a subset of patients with ALS possess mutations in the TDP-43 (TARDBP) gene. This further strengthens the hypotheses that gain of toxic function or loss of function in TDP-43 causes ALS. Currently, 29 different TARDBP missense mutations have been reported in 51 unrelated sporadic or familial ALS cases and two cases of ALS plus concomitant frontotemporal lobar degeneration with a remarkable concentration of mutations in the C-terminal glycine-rich domain of TDP-43. As these mutations will most certainly be an invaluable tool for the design and implementation of ALS animal and cell models, as well as serve as a platform for exploring the pathobiology of TDP-43, here we summarize the identified pathogenic TARDBP mutations and their potential impact on our understanding of the role of TDP-43 in disease.
Hum Mol Genet 2009 Oct 15
PMID:Mutations in TDP-43 link glycine-rich domain functions to amyotrophic lateral sclerosis. 1980 91

A membrane optode was developed utilizing the 8-hydroxyquinaldine (HQ) facilitated preconcentration of UO(2)(2+) ions and subsequent colored complex formation of UO(2)(2+) with 4-(2-thiazolylazo)-resorcinol (TAR) in optode matrix. The composition of the membrane optode was optimized by scanning several extractants immobilized in different plasticized polymer matrices. It was observed that the chelating agent HQ along with an indicator TAR immobilized in the tri-(2-ethylhexyl)phosphate (TEHP) plasticized cellulose triacetate matrix (CTA) was best suited as an optode for the UO(2)(2+) ions in aqueous samples. On sorption of UO(2)(2+) in the optode matrix, TAR changes color of the optode from yellow to magenta having a maximum absorbance (lambda(max)) at 546 nm. The uptake of UO(2)(2+) ions in the optode was found to be pH dependent and was maximum (>90%) at pH above 3. The acetate buffer (0.1 mol L(-1) sodium acetate + 0.1 mol L(-1) acetic acid) was found to be necessary for the stable response. The optimum equilibration time for the optode (2 cm x 1 cm) was found to be 30 min in 10 mL aqueous sample containing acetate buffer (pH 4.75). The equilibration time was found to increase with increase in aqueous sample volume. The optode response was found to be linear in the UO(2)(2+) ions concentration range of 0.01-0.11 micromol L(-1) in tap water as well as aqueous solutions containing 0.1 mol L(-1) NaCl or NaNO(3). The tolerance to the presence of several cations and anions in the determination of UO(2)(2+) ion was studied. It was observed that the optode in the presence of buffer can tolerate presence of large amounts of interfering cations (Ce(4+), V(4+), Eu(3+), Al(3+), Fe(3+), Ni(2+), Cd(2+), Co(2+), Pb(2+), Hg(2+), Cu(2+) and Th(4+) ions) without hindering the sorption of UO(2)(2+) ions in the optode matrix. The present work indicated that 50 ppb UO(2)(2+) ions in 100 mL sample can easily be quantified using this optode. The optode was found to be fully reversible, can readily be regenerated by equilibrating it with 0.1 mol L(-1) HNO(3) and reusable up to three cycles. The applicability of the developed optode in real samples was studied by determining uranium in the ground water samples spiked with a known quantity of UO(2)(2+) ions.
Spectrochim Acta A Mol Biomol Spectrosc 2009 Dec
PMID:Membrane optode for uranium(VI) ions preconcentration and quantification based on a synergistic combination of 4-(2-thiazolylazo)-resorcinol with 8-hydroxyquinaldine. 1987 85

In the male moth Agrotis ipsilon behavioural response and antennal lobe (AL) neuron sensitivity to the female-produced sex pheromone increase with age and juvenile hormone (JH) level. We recently showed that the neuromodulator, octopamine (OA), interacts with JH in this age-dependent olfactory plasticity. To further elucidate its role, we cloned a full cDNA encoding a protein that presents biochemical features essential to OA/tyramine receptor (AipsOAR/TAR) function. The AipsOAR/TAR transcript was detected predominantly in the antennae, the brain and, more specifically, in ALs where its expression level varied concomitantly with age. This expression plasticity indicates that AipsOAR/TAR might be involved in central processing of the pheromone signal during maturation of sexual behaviour in A. ipsilon.
Insect Mol Biol 2010 Aug
PMID:Cloning of an octopamine/tyramine receptor and plasticity of its expression as a function of adult sexual maturation in the male moth Agrotis ipsilon. 2049 82

The main function of the HIV-1 trans-activator of transcription (Tat protein) is to promote the transcription of the proviral DNA by the host RNA polymerase which leads to the synthesis of large quantities of the full length viral RNA. Tat is also thought to be involved in the reverse transcription (RTion) reaction by a still unknown mechanism. The recently reported nucleic acid annealing activity of Tat might explain, at least in part, its role in RTion. To further investigate this possibility, we carried out a fluorescence study on the mechanism by which the full length Tat protein (Tat(1-86)) and the basic peptide (44-61) direct the annealing of complementary viral DNA sequences representing the HIV-1 transactivation response element TAR, named dTAR and cTAR, essential for the early steps of RTion. Though both Tat(1-86) and the Tat(44-61) peptide were unable to melt the lower half of the cTAR stem, they strongly promoted cTAR/dTAR annealing through non-specific attraction between the peptide-bound oligonucleotides. Using cTAR and dTAR mutants, this Tat promoted-annealing was found to be nucleated through the thermally frayed 3'/5' termini, resulting in an intermediate with 12 intermolecular base pairs, which then converts into the final extended duplex. Moreover, we found that Tat(1-86) was as efficient as the nucleocapsid protein NCp7, a major nucleic acid chaperone of HIV-1, in promoting cTAR/dTAR annealing, and could act cooperatively with NCp7 during the annealing reaction. Taken together, our data are consistent with a role of Tat in the stimulation of the obligatory strand transfers during viral DNA synthesis by reverse transcriptase.
J Mol Biol 2010 Jul 16
PMID:The mechanism of HIV-1 Tat-directed nucleic acid annealing supports its role in reverse transcription. 2049 81


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