Constitutively active tyrosine kinases promote leukemogenesis by increasing cell proliferation and inhibiting apoptosis. However, mechanisms underlying apoptotic inhibition have not been fully elucidated. In many settings, apoptosis occurs by mitochondrial cytochrome c release, which nucleates the Apaf-1/caspase-9 apoptosome. Here we report that the leukemogenic kinases, Bcr-Abl, FLT3/D835Y, and Tel-PDGFRβ, all can inhibit apoptosome function. In cells expressing these kinases, the previously reported apoptosome inhibitor, Hsp90β, bound strongly to Apaf-1, preventing cytochrome c-induced Apaf-1 oligomerization and caspase-9 recruitment. Hsp90β interacted weakly with the apoptosome in untransformed cells. While Hsp90β was phosphorylated at Ser 226/Ser 255 in untransformed cells, phosphorylation was absent in leukemic cells. Expression of mutant Hsp90β (S226A/S255A), which mimics the hypophosphorylated form in leukemic cells, conferred resistance to cytochrome c-induced apoptosome activation in normal cells, reflecting enhanced binding of nonphosphorylatable Hsp90β to Apaf-1. In Bcr-Abl-positive mouse bone marrow cells, nonphosphorylatable Hsp90β expression conferred imatinib (Gleevec) resistance. These data provide an explanation for apoptosome inhibition by activated leukemogenic tyrosine kinases and suggest that alterations in Hsp90β-apoptosome interactions may contribute to chemoresistance in leukemias.
- American Society for Microbiology
- Inhibition of apoptosome formation by suppression of hsp90β ...
Identification of Archeological Remnants
Czorsztyn Castle, Poland 2D Electrical Imaging Objective Study area was within the ruins of the 14th century Czorsztyn Castle, located in the boundaries of Pieniny National Park (southern Poland). The main goal of this research was to check if one of the stone wall residues continues under the ground surface. Additionally, an attempt was made to identify other geoelectrical anomalies that may have archeological character by using the Geophysical Electrical Resistivity Tomography (ERT)imaging method. Layout Due...
Case Study - Panama Canal: Boat Towed 3D Resistivity Surveys
77 km Long 3D Canal Floor Sediment/Rock Study for Dredging EstimatesBoat towed streaming dipole-dipole resistivity data were successfully used to estimate geotechnical properties of the canal floor in order to reduce dredging costs for an ongoing Panama Canal expansion program.Site: The 77-km long Panama Canal with 773 line-km of resistivity data collected at 25 m transect spacing inside the canal(fresh water) and then out into the Pacific and Caribbean approach areas (salt water).Instrument: SuperStingR8 with...
Case Study - Lacustrine: Underwater Resistivity Surveys
Lake Travis – Austin, TexasObjective: Locate buried pipeline and map the limestone bedrock surfaceSite: Lake Travis, near Austin, Texas USA during the AGI Marine Resistivity SeminarDate: May 1, 2014 and May 7, 2015Instrument: SuperStingR8 WiFi, SwitchBox56, underwater marine cable with 28 electrodes spaced at 6m.Software: EarthImager 2D underwater resistivity inversion model incorporating bathymetry and water conductivity dataResult: Underwater resistivity imaging mapped the limestone bedrock and located...
Case Study - Shallow Soil Resistivity Survey
Lima, PeruSite: Pontificia Universidad Católica del Perú, Lima, PeruInstrument and method: SuperStingR8 WiFi with 28 electrode passive electrical imaging cable. Measured in dipole-dipole and inverse schlumberger array. Modeled with EarthImager 2D.Results: Resistivity data were used to successfully estimate the thickness of a soil layer that was added to retain moisture and allow grass to grow. The location of a concrete foundation was determined and also the extent that roots have grown outwards...
Case Study - Construction Aggregate: Sand
Geologic Mapping of Sand Unit ThicknessPyramid was contracted to perform an electrical resistivity survey across 230 acres of undeveloped land in North Carolina. The purpose of the survey was to quantify the lateral extents and approximate depth/thicknesses of sandy soils near the ground surface. The client was interested in the potential of the site to be utilized as a sand mine, and wanted to understand the potential yield of sandy soils at the property.Prior to the geophysical survey, shallow soil borings were...