Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transcriptional regulation of human establishment of cohesion 1 homolog 2 (ESCO2), the causative gene of Roberts syndrome, was investigated. Deletion and mutation analyses of the ESCO2 promoter indicated that the selenocysteine tRNA-activating factor (Staf) binding site (SBS) is an essential element for transcriptional activation of ESCO2. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay revealed that the zinc finger protein 143 (ZNF143), a human homolog of Xenopus Staf, bound to the ESCO2 promoter. The ACTACAN submotif, adjacent to SBS, also contributed to transcriptional activation of ESCO2. EMSA indicated that the ACTACAN submotif was not involved in binding of ZNF143 to SBS. S phase-specific expression of the ESCO2 gene was confirmed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR), but EMSA revealed binding of ZNF143 to SBS in G1/S and G2/M phases. These results demonstrated that SBS functioned as the basal transcriptional activator of the S phase-specific gene ESCO2, but other mechanisms are required for cell cycle-dependent expression.
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PMID:Transcriptional regulation of the human establishment of cohesion 1 homolog 2 gene. 2011 66

Accelerated neurological disorders are increasingly prominent among the HIV-infected population and are likely driven by the toxicity from long-term use of antiretroviral drugs. We explored potential side effects of antiretroviral drugs in HIV-infected primary human astrocytes and whether opioid co-exposure exacerbates the response. HIV-infected human astrocytes were exposed to the reverse transcriptase inhibitor, emtricitabine, alone or in combination with two protease inhibitors ritonavir and atazanavir (ERA) with and without morphine co-exposure. The effect of the protease inhibitor, lopinavir, alone or in combination with the protease inhibitor, abacavir, and the integrase inhibitor, raltegravir (LAR), with and without morphine co-exposure was also explored. Exposure with emtricitabine alone or ERA in HIV-infected astrocytes caused a significant decrease in viral replication and attenuated HIV-induced inflammatory molecules, while co-exposure with morphine negated the inhibitory effects of ERA, leading to increased viral replication and inflammatory molecules. Exposure with emtricitabine alone or in combination with morphine caused a significant disruption of mitochondrial membrane integrity. Genetic analysis revealed a significant increase in the expression of p62/SQSTM1 which correlated with an increase in the histone-modifying enzyme, ESCO2, after exposure with ERA alone or in combination with morphine. Furthermore, several histone-modifying enzymes such as CIITA, PRMT8, and HDAC10 were also increased with LAR exposure alone or in combination with morphine. Accumulation of p62/SQSTM1 is indicative of dysfunctional lysosomal fusion. Together with the loss of mitochondrial integrity and epigenetic changes, these effects may lead to enhanced viral titer and inflammatory molecules contributing to the neuropathology associated with HIV.
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PMID:Morphine counteracts the antiviral effect of antiretroviral drugs and causes upregulation of p62/SQSTM1 and histone-modifying enzymes in HIV-infected astrocytes. 3074 9