E3 Ligase Activity of XIAP RING Domain Is Required for XIAP-Mediated Cancer Cell Migration, but Not for Its RhoGDI Binding Activity

Although an increased expression level of XIAP is associated with cancer cell metastasis, the underlying molecular mechanisms remain largely unexplored. To verify the specific structural basis of XIAP for regulation of cancer cell migration, we introduced different XIAP domains into XIAP−/− HCT116 cells, and found that reconstitutive expression of full length HA-XIAP and HA-XIAP ΔBIR, both of which have intact RING domain, restored β-Actin expression, actin polymerization and cancer cell motility. Whereas introduction of HA-XIAP ΔRING or H467A mutant, which abolished its E3 ligase function, did not show obvious restoration, demonstrating that E3 ligase activity of XIAP RING domain played a crucial role of XIAP in regulation of cancer cell motility. Moreover, RING domain rather than BIR domain was required for interaction with RhoGDI independent on its E3 ligase activity. To sum up, our present studies found that role of XIAP in regulating cellular motility was uncoupled from its caspase-inhibitory properties, but related to physical interaction between RhoGDI and its RING domain. Although E3 ligase activity of RING domain contributed to cell migration, it was not involved in RhoGDI binding nor its ubiquitinational modification

A Green Bank Telescope Search for Narrowband Technosignatures between 1.1 and 1.9 GHz During 12 Kepler Planetary Transits

Agrowing avenue for determining the prevalence of life beyond Earth is to search for “technosignatures” from extraterrestrial intelligences/agents. Technosignatures require significant energy to be visible across interstellar space and thus intentional signals might be concentrated in frequency, in time, or in space, to be found in mutually obvious places. Therefore, it could be advantageous to search for technosignatures in parts of parameter space that are mutually derivable to an observer on Earth and a distant transmitter. In this work, we used the L -band (1.1–1.9 GHz) receiver on the Robert C. Byrd Green Bank Telescope to perform the first technosignature search presynchronized with exoplanet transits, covering 12 Kepler systems. We used the Breakthrough Listen turboSETI pipeline to flag narrowband hits (∼3 Hz) using a maximum drift rate of ±614.4 Hz s ^−1 and a signal-to-noise threshold of 5—the pipeline returned ∼3.4 × 10 ^5 apparently-localized features. Visual inspection by a team of citizen scientists ruled out 99.6% of them. Further analysis found two signals of interest that warrant follow up, but no technosignatures. If the signals of interest are not redetected in future work, it will imply that the 12 targets in the search are not producing transit-aligned signals from 1.1 to 1.9 GHz with transmitter powers >60 times that of the former Arecibo radar. This search debuts a range of innovative technosignature techniques: citizen science vetting of potential signals of interest, a sensitivity-aware search out to extremely high drift rates, a more flexible method of analyzing on-off cadences, and an extremely low signal-to-noise threshold