Mdm2 Induces Mono-Ubiquitination of FOXO4

Background: The Forkhead box O (FOXO) class of transcription factors are involved in the regulation of several cellular responses including cell cycle progression and apoptosis. Furthermore, in model organisms FOXOs act as tumor suppressors and affect aging. Previously, we noted that FOXOs and p53 are remarkably similar within their spectrum of regulatory proteins [1]. For example, the de-ubiquitinating enzyme USP7 removes ubiquitin from both FOXO and p53. However, Skp2 has been identified as E3 ligase for FOXO1, whereas Mdm2 is the prime E3 ligase for p53. Principal Findings/Methodology: Here we provide evidence that Mdm2 acts as an E3 ligase for FOXO as well. In vitro incubation of Mdm2 and FOXO results in ATP-dependent (multi)mono-ubiquitination of FOXO similar to p53. Furthermore, in vivo co-expression of Mdm2 and FOXO induces FOXO mono-ubiquitination and consistent with this result, siRNAmediated depletion of Mdm2 inhibits mono-ubiquitination of FOXO induced by hydrogen peroxide. Regulation of FOXO ubiquitination by Mdm2 is likely to be direct since Mdm2 and FOXO co-immunoprecipitate. In addition, Mdm2-mediated ubiquitination regulates FOXO transcriptional activity. Conclusions/Significance: These data identify Mdm2 as a novel E3 ligase for FOXOs and extend the analogous mode o

Adsorption and two-body recombination of atomic hydrogen on 3^3He-4^4He mixture films

We present the first systematic measurement of the binding energy $E_a$ of hydrogen atoms to the surface of saturated $^3$He-$^4$He mixture films. $E_a$ is found to decrease almost linearly from 1.14(1) K down to 0.39(1) K, when the population of the ground surface state of $^3$He grows from zero to $6\times10^{14}$ cm$^{-2}$, yielding the value $1.2(1)\times 10^{-15}$ K cm$^2$ for the mean-field parameter of H-$^3$He interaction in 2D. The experiments were carried out with overall $^3$He concentrations ranging from 0.1 ppm to 5 % as well as with commercial and isotopically purified $^4$He at temperatures 70...400 mK. Measuring by ESR the rate constants $K_{aa}$ and $K_{ab}$ for second-order recombination of hydrogen atoms in hyperfine states $a$ and $b$ we find the ratio $K_{ab}/K_{aa}$ to be independent of the $^3$He content and to grow with temperature.Comment: 4 pages, 4 figures, all zipped in a sigle file. Submitted to Phys. Rev. Let

Wannier-function description of the electronic polarization and infrared absorption of high-pressure hydrogen

We have constructed maximally-localized Wannier functions for prototype structures of solid molecular hydrogen under pressure, starting from LDA and tight-binding Bloch wave functions. Each occupied Wannier function can be associated with two paired protons, defining a ``Wannier molecule''. The sum of the dipole moments of these ``molecules'' always gives the correct macroscopic polarization, even under strong compression, when the overlap between nearby Wannier functions becomes significant. We find that at megabar pressures the contributions to the dipoles arising from the overlapping tails of the Wannier functions is very large. The strong vibron infrared absorption experimentally observed in phase III, above ~ 150 GPa, is analyzed in terms of the vibron-induced fluctuations of the Wannier dipoles. We decompose these fluctuations into ``static'' and ``dynamical'' contributions, and find that at such high densities the latter term, which increases much more steeply with pressure, is dominant.Comment: 17 pages, two-column style with 14 postscript figures embedded. Uses REVTEX and epsf macro