335,436 research outputs found

    PPM1D phosphatase, a target of p53 and RBM38 RNA-binding protein, inhibits p53 mRNA translation via dephosphorylation of RBM38.

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    PPM1D phosphatase, also called wild-type p53-induced phosphatase 1, promotes tumor development by inactivating the p53 tumor suppressor pathway. RBM38 RNA-binding protein, also called RNPC1 and a target of p53, inhibits p53 messenger RNA (mRNA) translation, which can be reversed by GSK3 protein kinase via phosphorylation of RBM38 at serine 195. Here we showed that ectopic expression of RBM38 increases, whereas knockdown of RBM38 inhibits, PPM1D mRNA translation. Consistent with this, we found that RBM38 directly binds to PPM1D 3'-untranslated region (3'-UTR) and promotes expression of a heterologous reporter gene that carries PPM1D 3'-UTR in a dose-dependent manner. Interestingly, we showed that PPM1D directly interacts with and dephosphorylates RBM38 at serine 195. Furthermore, we showed that PPM1D modulates p53 mRNA translation and p53-dependent growth suppression through dephosphorylation of RBM38. These findings provide evidence that the crosstalk between PPM1D and RBM38, both of which are targets and modulators of p53, has a critical role in p53 expression and activity

    Holographic Thermalization in Charged Dilaton Anti-de Sitter Spacetime

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    We study holographic thermalization in spacetimes with a chemical potential and a non-trivial dilaton field. Three non-local observables are used to probe the whole process and investigate the effect of the ratio of the chemical potential over temperature χ\chi and the dilaton-Maxwell coupling constant α\alpha. It is found that the saturation time is not always a monotonically increasing function of χ\chi, the situation depends on α\alpha. When 0α10 \leq\alpha \leq 1, larger χ\chi yields longer saturation time, while for α>1\alpha>1, the situation becomes more complex. More interesting, we found that although α\alpha indeed has influence on the whole thermalization process, it nearly does not affect the saturation time, which indicates the universality of the saturation time for the dual one-parameter field theories.Comment: 22 pages, 5 figure

    Singularity points for first passage percolation

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    Let 0<a<b<0<a<b<\infty be fixed scalars. Assign independently to each edge in the lattice Z2\mathbb{Z}^2 the value aa with probability pp or the value bb with probability 1p1-p. For all u,vZ2u,v\in\mathbb{Z}^2, let T(u,v)T(u,v) denote the first passage time between uu and vv. We show that there are points xR2x\in\mathbb{R}^2 such that the ``time constant'' in the direction of xx, namely, limnn1Ep[T(0,nx)],\lim_{n\to\infty}n^{-1}\mathbf{E}_p[T(\mathbf{0},nx)], is not a three times differentiable function of pp.Comment: Published at http://dx.doi.org/10.1214/009117905000000819 in the Annals of Probability (http://www.imstat.org/aop/) by the Institute of Mathematical Statistics (http://www.imstat.org
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