Regulation of p53 pathway and Tumor Growth by Novel Nucleolar Protein PICT1

肿瘤抑制MDM2-p53细胞内信号通路被细胞应激激活。这种压力包括DNA损伤，它会触发ATM-Chk2和ATR-Chk1级联反应；感染或癌基因激活，从而诱导p19ARF通路；核核体应激启动核糖体蛋白（RPs）介导的级联反应，尤其是RPL5、RPL11、RPL23和RPS7。这些RPs通常位于核仁中，但在核仁应激时迅速释放到核质中，激活MDM2-p53通路。然而，p53激活的RP基因与体内癌症发展之间是否存在直接联系，以及这些RP在应激反应中从核核向核质转移的机制尚不清楚。通过涉及人类和小鼠组织的体内和体外实验，我们发现新基因Pict1是通过RP控制MDM2-p53对核仁应激反应的关键调节因子。此外，Pict1的表达与人类结肠癌的进展相关。

The tumor-suppressive MDM2-p53 intracellular signaling pathway is activated by cellular stress. Such stress includes DNA damage, which triggers the ATM-Chk2 and ATR-Chk1 cascades ; infection or oncogene activation, which induce t he p19ARF pathway ; and nucleolar stress, which initiates a cascade mediated by ribosomal proteins (RPs), particularly RPL5, RPL11, RPL23, and RPS7. These RPs are usually located in the nucleolus but are rapidly released into the nucleoplasm upon nucleolar stress, activating the MDM2-p53 pathway. However , it is unknown whether there are direct connections between p53-activating RP genes and cancer development in vivo, and which mechanism these RPs emplo y to translocate from the nucleolus to the nucleoplasm in response to stress . Using in vivo and in vitro experiments involving both human and murine tissues, we show that novel gene, Pict1, is a key regulator that acts thro ugh RP to control MDM2-p53 responses to nucleolar stress. In addition, Pict1 expression correlates with human colon cancer progression in human.