2011.04.21,Professor Wang Guanghui Published a paper in JBC

  • 2011.04.21,Professor Wang Guanghui published a paper entitled “Dysbindin-1, a schizophrenia-related protein, facilitates neurite outgrowth by promoting the transcriptional activity of p53” in Molecular Psychiatry 

    Author:Ma Xiaochuang,Fei Erkang,Fu Cheng,Ren  Haigang,Wang Guanghui

    Abstract

    Genetic variations in the DTNBP1 gene (encoding the protein dysbindin-1) have been implicated as risk factors in the pathogenesis of schizophrenia. Previous studies have indicated that dysbindin-1 functions in the regulation of synaptic activity. Recently, dysbindin-1 has also been documented to be involved in neuronal development. In this study, we identified necdin as a binding partner of dysbindin-1 using a yeast two-hybrid screen. Dysbindin-1 recruits necdin to the cytoplasm, thereby attenuating the repressive effects of necdin on p53 transcriptional activity. Knockdown of dysbindin-1, like knockdown of p53, greatly decreases the expressions of the p53 target genes Coronin 1b and Rab13, which are required for neurite outgrowth. Moreover, overexpression of p53 restores the neurite outgrowth blocked by dysbindin-1 knockdown. In brains of dysbindin-1 null mice (the sandy strain), p21, Coronin 1b and Rab13 levels are reduced. Furthermore, primary cultured cortical neurons from sandy mice display neurite outgrowth defects when compared with those from wild-type mice. Thus, our data provide evidence that dysbindin-1 plays an important role in neurite outgrowth through its regulation of p53’s transcriptional activity.

     

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