【摘要】 Cdh1是后期促进因子APC复合物的共激活因子之一,其蛋白在有丝分裂末期和G0/G1期激活APC复合物.Cdh1通过识别特异性的序列,在特定的细胞周期时刻为APC复合物呈递需要被降解的底物.Sp100作为PML-NBs结构重要组成蛋白,参与抗病毒,转录调控,细胞凋亡等重要的细胞活动.在本课题组前期研究工作中,发现了Sp100的蛋白序列上含有一个典型的D-box序列,即RxxL,暗示着Sp100能够被Cdh1识别,可能是APC复合物的底物.在本实验中,证明了Cdh1参与Sp100蛋白泛素化降解的途径,并且这个过程依赖于Sp100蛋白完整的D-box结构.这些发现不仅提供了一种新的内源的Sp100蛋白调控方式,并且为进一步研究Sp100以及其他PML-NBs蛋白的调节打下基础.更多还原

【Abstract】 As a co-activator of the APC/C complex,Cdh1 recruit substrates at particular cycle phases and mediate their degradation.PML-NBs are nucleolar domains that present as nuclear particles in interphase and disperse during mitosis.Sp100 is a PML-NB scaffold protein that participates in viral resistance,transcriptional regulation,and apoptosis.However,its metabolism during the cell cychas not yet been clarified.We found a putative D-box in Sp100 using the eukaryotic linear motif assay.Furthermore,Cdh1 mediated the degradation of Sp100 through the ubiquitination pathway,and the intact D-box of Sp100 was necessary for this process.更多还原