真核生物基因转录和翻译分别在细胞核和细胞质中进行，大多数新合成的mRNA要经过3' Poly(A)化才能被运输出核进而在细胞质中完成翻译。一类Poly(A)结合蛋白（PABP）能特异结合mRNA Poly(A)参与基因表达调控，其中以PABP1研究较多。PABP1在核内与Poly(A) 结合并转运mRNA出核，在细胞质中参与蛋白质翻译启动。我们初步发现PABP1可能在p53的转录活性、mdm2蛋白降解和细胞自噬方面有新功能；并检测到乙酰化和磷酸化修饰位点突变能明显改变PABP1核质转运；还鉴定到一个新PABP蛋白。我们计划研究：PABP1核质转运调控机制；PABP在肿瘤细胞凋亡、自噬和耐药耐辐射方面的新功能；肿瘤细胞内去乙酰化酶SirT1异常细胞质分布对PABP1功能影响；并研究我们发现的新PABP蛋白功能。该研究有助于深化了解真核生物复杂的基因表达调控过程，为肿瘤治疗提供理论基础。

In eukaryotes, transcription and translation take place in nucleus and cytoplasm separately. Most known mRNAs are polyadenylated at their 3' ends in nucleus and then translocated to cytoplasm for protein translation. PABP is a family of poly(A)-binding proteins that binds to mRNA poly(A) tail with high specificity. Accumulating data has revealed that a member of this family, PABP1, is required for mRNA nucleus-cytoplasm transportation, mRNA stability and translation initiation. Our primary data showed PABP1 may also have novel functions in regulating p53 transcriptional activity, mdm2 degradation and autophagy. Moreover, we identified that post-transcriptional modification of PABP1, including phosphorylation and acetylation, may bridle the shuttling of PABP1 between nucleus and cytoplasm. Furthermore, we identified a novel PABP protein. We thus propose to study the mechanism and new functions of PABP1 in regulating apoptosis, autophagy, and the radiation- and drug-resistance of cancer cells. We also plan to study the function of cytoplsm located SirT1 in PABP1 regulation in some cancer cells. Finally, we will study functions of the identified PABP isoform. Our project will contribute to understand the mechanism of how eukaryotes finely regulate the gene expression at different levels and provide new strategy for tumor therapy.