Molecular targets of HIV integrase inhibitor, MK-2048, on ATL cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA450607 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Adult T-cell Leukemia (ATL) is a highly chemoresistant malignancy of peripheral T lymphocytes, associated with retrovirus human T-cell leukemia virus type I (HTLV-1). To elucidate the complex molecular mechanism of anti-Growth effect of the HIV integrase inhibitor, MK-2048 in ATL cells, we attempted to perform gene expression profiling.
2020-01-01 | GSE113265 | GEO
Project description:MK-2048 represents a prototype second-generation integrase strand transfer inhibitor (INSTI) developed with the goal of retaining activity against viruses containing mutations associated with resistance to first-generation INSTIs, raltegravir (RAL) and elvitegravir (EVG). Here, we report the identification of mutations (G118R and E138K) which confer resistance to MK-2048 and not to RAL or EVG. These mutations were selected in vitro and confirmed by site-specific mutagenesis. G118R, which appeared first in cell culture, conferred low levels of resistance to MK-2048. G118R also reduced viral replication capacity to approximately 1% that of the isogenic wild-type (wt) virus. The subsequent selection of E138K partially restored replication capacity to approximately 13% of wt levels and increased resistance to MK-2048 to approximately 8-fold. Viruses containing G118R and E138K remained largely susceptible to both RAL and EVG, suggesting a unique interaction between this second-generation INSTI and the enzyme may be defined by these residues as a potential basis for the increased intrinsic affinity and longer "off" rate of MK-2048. In silico structural analysis suggests that the introduction of a positively charged arginine at position 118, near the catalytic amino acid 116, might decrease Mg(2+) binding, compromising enzyme function and thus leading to the significant reduction in both integration and viral replication capacity observed with these mutations.
| S-EPMC2937597 | biostudies-literature
Project description:Adult T-cell leukemia (ATL) is a fatal neoplasia derived from HTLV-1 infected T lymphocytes exhibiting constitutive activation of NF-kB. To elucidate the complex molecular mechanism of anti-tumor effect of the proteasome inhibitor, bortezomib in ATL cells, we attempted to perform gene expression profiling. Keywords: dose response
2007-10-09 | GSE6034 | GEO
Project description:Identification of minority resistance mutations in the HIV-1 integrase gene using Next Generation Sequencing
| PRJEB9552 | ENA
Project description:MK: MK-801. Young male C57BL/6J mice received an injection of MK-801 (300 micro-g per g body weight). RNA from control mice were extracted 1hr, 2hr, 4hr, and 6hr after MK experimental mice received their last shock treatment. MK C+S: MK-801 & Context + Shock: Young male C57BL/6J mice received an injection of MK-801 (300 micro-g per g body weight) 1 h prior to contextual fear conditioning that consisted of: Placement into a novel spatial context for 2 min. After 2 min, a 1 sec (0.5 mA) shock was administered through a floor grid. The 2 min-1 sec shock paradigm was repeated for a total of 3 shocks. 1 min after the last shock, animals were removed to their homecage. RNA was extracted 1hr, 2hr, 4hr, and 6hr after the last shock treatment. Keywords: time-course
2003-02-27 | GSE318 | GEO
Project description:MK: MK-801. Young male C57BL/6J mice received an injection of MK-801 (300 micro-g per g body weight). RNA from control mice were extracted 1hr, 2hr, 4hr, and 6hr after MK experimental mice received their last shock treatment. MK C+S: MK-801 & Context + Shock: Young male C57BL/6J mice received an injection of MK-801 (300 micro-g per g body weight) 1 h prior to contextual fear conditioning that consisted of: Placement into a novel spatial context for 2 min. After 2 min, a 1 sec (0.5 mA) shock was administered through a floor grid. The 2 min-1 sec shock paradigm was repeated for a total of 3 shocks. 1 min after the last shock, animals were removed to their homecage. RNA was extracted 1hr, 2hr, 4hr, and 6hr after the last shock treatment. Keywords: time-course
2003-02-27 | GSE317 | GEO
Project description:Integrase CLIP-seq experiments were conducted on wild-type and eccentric HIV-1 virions generated in the presence of allosteric integrase inhibitors and IN K264/266A and R269/K273A mutations Integrase CLIP-seq experiments were conducted by immunoprecipitation of integrase-RNA complexes from fully formed mature and eccentric virus particles. Libraries of RNA molecules bound by integrase were generated and sequenced by Illumina Hi-Seq2000 and 2500 platforms.
2016-08-25 | E-GEOD-83588 | biostudies-arrayexpress
Project description:Integrase CLIP-seq experiments were conducted on wild-type and eccentric HIV-1 virions generated in the presence of allosteric integrase inhibitors and IN K264/266A and R269/K273A mutations
2016-08-25 | GSE83588 | GEO
Project description:Bacillus mycoides DSM 2048 Genome sequencing
| PRJNA814637 | ENA
Project description:Populus trichocarpa 2048-3 Resequencing
| PRJNA499780 | ENA