The Regulatory Mechanism Study Of Nuclear IASPP In Regulating Tumor Cell Apoptosis

iASPP is a well-known oncogene,and previous studies in the laboratory have found that in the case of cell apoptosis,the iASPP protein in the cytoplasm will be cleaved by caspase3 protein to form a truncated body,and iASPP(295-828)can interact with p53 The protein and NF-kappaB protein are combined.The p53 signaling pathway and the NF-kappaB signaling pathway play a vital role in cellular stress response,and the two signaling pathways are often intertwined,but they play opposite biological functions.Therefore,it is of great significance to explore the interaction between iASPP(295-828)and the p53 signaling pathway and the NF-kappaB signaling pathway.This article mainly explores the effect of iASPP(295-828)on tumor cell apoptosis under different p53 and NF-kappaB activation conditions.Firstly,MCF-7 tumor cells were treated with Nutlin-3 drug to complete the establishment of p53 single activation model,and verified by Western Blot method and Luciferase reporter assay method.Apoptosis experiments show that under the condition of single activation of p53,iASPP(295-828)can inhibit the apoptosis of MCF-7 tumor cells by inhibiting the activity of p53.Secondly,in MCF-7 tumor cells,treated with TNF-α drugs,the establishment of the single activation model of NF-kappaB was completed,and it was verified by Western Blot method and Luciferase reporter assay method.Apoptosis experiments show that under the condition of single activation of NF-kappaB,iASPP(295-828)can promote the apoptosis of MCF-7 tumor cells by inhibiting the activity of NF-kappaB.Thirdly,in SK-BR3 tumor cells,a cell line in which NF-kappaB is continuously activated.Apoptosis experiments show that iASPP(295-828)promotes the apoptosis of SK-BR3 tumor cells by inhibiting NF-kappaB activity to a greater extent.Finally,in RKO tumor cells,treated with Act D drugs,the establishment of the co-activation model of p53 and NF-kappaB was completed,and the Western Blot method and Luciferase reporter assay method were used to verify.The CHIP experiment showed that under the co-activation condition of p53 and NF-kappaB,iASPP(295-828)inhibited the transcription factor activity of p53 to a greater extent.At the same time,the apoptosis experiment showed that under the co-activation condition of p53 and NF-kappaB,the iASPP(295-828)inhibited the apoptosis of RKO tumor cells by inhibiting the activity of p53 transcription factors to a greater extent.This article basically explored the effects of p53 single activation,NF-kappaB single activation,and p53 and NF-kappaB co-activation,iASPP(295-828)on p53 activity,NF-kappaB activity and tumor cell apoptosis.These conclusions provide more important new insights for iASPP to regulate the activity of p53 and NF-kappaB,and at the same time provide guidance for the development of iASPP targeted therapy,which is of great significance for cancer treatment.