The Dkk3 gene encodes a vital intracellular regulator of cell proliferation

Members of the Dickkopf (Dkk) family of Wnt antagonists interrupt Wnt-induced receptor assembly and participate in axial patterning and cell fate determination. One family member, DKK3, does not block Wnt receptor activation. Loss of Dkk3 expression in cancer is associated with hyperproliferation and dysregulated ss-catenin signaling, and ectopic expression of Dkk3 halts cancer growth. The molecular events mediating the DKK3-dependent arrest of ss-catenin-driven cell proliferation in cancer cells are unknown. Here we report the identification of a new intracellular gene product originating from the Dkk3 locus. This Dkk3b transcript originates from a second transcriptional start site located in intron 2 of the Dkk3 gene. It is essential for early mouse development and is a newly recognized regulator of ss-catenin signaling and cell proliferation. Dkk3b interrupts nuclear translocation ss-catenin by capturing cytoplasmic, unphosphorylated ss-catenin in an extra-nuclear complex with ss-TrCP. These data reveal a new regulator of one of the most studied signal transduction pathways in metazoans and provides a novel, completely untapped therapeutic target for silencing the aberrant ss-catenin signaling that drives hyperproliferation in many cancers

Quantum Magnetism of Spin-Ladder Compounds with Trapped-Ion Crystals

The quest for experimental platforms that allow for the exploration, and even control, of the interplay of low dimensionality and frustration is a fundamental challenge in several fields of quantum many-body physics, such as quantum magnetism. Here, we propose the use of cold crystals of trapped ions to study a variety of frustrated quantum spin ladders. By optimizing the trap geometry, we show how to tailor the low dimensionality of the models by changing the number of legs of the ladders. Combined with a method for selectively hiding of ions provided by laser addressing, it becomes possible to synthesize stripes of both triangular and Kagome lattices. Besides, the degree of frustration of the phonon-mediated spin interactions can be controlled by shaping the trap frequencies. We support our theoretical considerations by initial experiments with planar ion crystals, where a high and tunable anisotropy of the radial trap frequencies is demonstrated. We take into account an extensive list of possible error sources under typical experimental conditions, and describe explicit regimes that guarantee the validity of our scheme

Kommentar zum gesetz betreffend die gesellschaften mit beschränkter haftung. Nebst einem anhange: Das österreichische gesetz über die gesellschaften mit beschränkter haftung.

Mode of access: Internet

Characterization of the DKK3b:ß-TrCP:ß-catenin complex and its effects of ß-catenin nuclear translocation/signaling.

<p>(A) Co-IP of DKK3b, ß-TrCP and ß-^S33Ycatenin from HEK293 cell lysates. Epitope tagged targets were expressed by transient transfection in HEK293 cells, immune precipitates collected by Protein A/G Sepharose, and co-precipitating partners were analyzed by immunoblot with epitope specific antibodies. (B) Co-IP of HEK293 cell lysates lacking one binding partner. (C) shRNA knockdown of ß-TrCP in HeLa cells. Immunoblots done with anti-TrCP IgG. (D) Effects of <i>ß-TrCP</i> KD and ß-TrCP rescue on TAT-DKK3b dependent inhibition of TOPflash activity in HeLa cells. Unaltered, non-silencing control, <i>ß-TrCP</i> KD cells, and rescued <i>ß-TrCP</i> KD cells expressing a mouse ß-TrCP rescue plasmid were stimulated with ±LiCl for 16h in the absence or presence of TAT-DKK3b (5 μg/ml). TOPflash activity reported as fold change from resting HeLa cells. Data are reported as the means ± se (n = 4); each experiment was repeated 3 times.</p