14-3-3ζ Interacts with Stat3 and Regulates Its Constitutive Activation in Multiple Myeloma Cells

The 14-3-3 proteins are a family of regulatory signaling molecules that interact with other proteins in a phosphorylation-dependent manner and function as adapter or scaffold proteins in signal transduction pathways. One family member, 14-3-3ζ, is believed to function in cell signaling, cycle control, and apoptotic death. A systematic proteomic analysis done in our laboratory has identified signal transducers and activators of transcription 3 (Stat3) as a novel 14-3-3ζ interacting protein. Following our initial finding, in this study, we provide evidence that 14-3-3ζ interacts physically with Stat3. We further demonstrate that phosphorylation of Stat3 at Ser727 is vital for 14-3-3ζ interaction and mutation of Ser727 to Alanine abolished 14-3-3ζ/Stat3 association. Inhibition of 14-3-3ζ protein expression in U266 cells inhibited Stat3 Ser727 phosphorylation and nuclear translocation, and decreased both Stat3 DNA binding and transcriptional activity. Moreover, 14-3-3ζ is involved in the regulation of protein kinase C (PKC) activity and 14-3-3ζ binding to Stat3 protects Ser727 dephosphorylation from protein phosphatase 2A (PP2A). Taken together, our findings support the model that multiple signaling events impinge on Stat3 and that 14-3-3ζ serves as an essential coordinator for different pathways to regulate Stat3 activation and function in MM cells

Analysis of polyaddition levels in i-Sc3NC80.

Using the density functional method, the stabilities of highly hydrogenated and fluorinated [80]fullerenes, both empty and containing the Sc3N molecule, have been calculated. Addition of 44 atoms to i-Sc3NC80 is predicted to be most favorable due to the formation of six octahedrally located benzenoid rings, while addition of up to 52 atoms (consistent with preliminary fluorination data) gives a structure stabilized by the presence of four benzenoid rings. The most stable isomers at this addition level have been determined and the relative stabilities of a number of C80H52, C80F52, and i-Sc3NC80H52 species calculated. The hydrogenation of the i-Sc3NC80 has been computed to be more difficult than the corresponding partner, C80. From the geometrical point of view, the Sc3N molecule is planar in the parent [80]fullerene but is calculated to be pyramidal in some of the hydrogenated/fluorinated derivatives. Moreover, in these it has fixed locations due to orbital interactions arising from deformation of the cage and the presence of localized double bonds

Analysis of polyaddition levels in i-Sc3NC80.

Using the density functional method, the stabilities of highly hydrogenated and fluorinated [80]fullerenes, both empty and containing the Sc3N molecule, have been calculated. Addition of 44 atoms to i-Sc3NC80 is predicted to be most favorable due to the formation of six octahedrally located benzenoid rings, while addition of up to 52 atoms (consistent with preliminary fluorination data) gives a structure stabilized by the presence of four benzenoid rings. The most stable isomers at this addition level have been determined and the relative stabilities of a number of C80H52, C80F52, and i-Sc3NC80H52 species calculated. The hydrogenation of the i-Sc3NC80 has been computed to be more difficult than the corresponding partner, C80. From the geometrical point of view, the Sc3N molecule is planar in the parent [80]fullerene but is calculated to be pyramidal in some of the hydrogenated/fluorinated derivatives. Moreover, in these it has fixed locations due to orbital interactions arising from deformation of the cage and the presence of localized double bonds

Density functional calculations on the intricacies of Moiré patterns on graphite

Scanning tunneling microscopy (STM) imaging has detected a wealth of puzzling features on the surface of highly oriented pyrolytic graphite, among them, anomalously large superperiodicities, called Moiré patterns, caused by the lattice-mismatched top layer of graphite. Exactly, the top graphene layer rotates with respect to the graphite substrate. Such rotation gives rise to different types of local stackings in the different surface graphite regions. As STM mapping is highly dependent on the differences of local density of states of the graphite surface at the Fermi level, variations in brightness differentiate graphite regions with different local stackings. Bright areas (visible graphite areas) correspond to AABABAB... local graphite stackings, whereas dark areas (hidden graphite areas) to BABABAB... or CABABAB... ones. We have programmed an algorithm which first built systematically the whole range of Moiré structures and afterwards quantified the percentages of the different local graphite stackings. Finally, periodic density functional theory calculations have been performed on a selection of Moiré structures in order to draw the energy profile of the rotation between two graphene layers. © 2007 The American Physical Society

Open-cage fullerene derivatives with 15-membered-ring orifices.

The addition reaction of the N-MEM-ketolactam derivative of [60]fullerene with phenyl, p-Br-phenyl, and p-MeO-phenyl hydrazines proceeds regioselectively, affording three open-cage fullerene derivatives bearing a 15-membered-ring orifice on the fullerene cage. Both experimental data and theoretical calculations were utilized for the structure determination of the new [60]fullerene adducts

Open-cage fullerene derivatives with 15-membered-ring orifices.

The addition reaction of the N-MEM-ketolactam derivative of [60]fullerene with phenyl, p-Br-phenyl, and p-MeO-phenyl hydrazines proceeds regioselectively, affording three open-cage fullerene derivatives bearing a 15-membered-ring orifice on the fullerene cage. Both experimental data and theoretical calculations were utilized for the structure determination of the new [60]fullerene adducts

Dislocations of Burgers vector c/2 in graphite

We report calculations in support of the application of LDA within DFT to graphite and go on to report the inner core structure and energetics of prismatic dislocations with Burgers vector c/2: two types of edge and one of screw type. We find the screw dislocations preserve sp2 hybridisation and graphite bonding, whereas one edge type (zigzag) gives rise to interlayer single bonds and sp3 hybridisation, while the other type (armchair) does not, preferring instead to rehybridise towards sp and form bonds with itself approaching triple character. For computational and physical reasons these calculations were based on AA graphite, rather than Bernal (AB) graphite. © 2007 WILEY-VCH Verlag GmbH & Co. KGaA