The Role of Zinc Finger Structure Transcription Factors ZNF148 and SP5 on P53 Transcriptional Activity
10.13865/j.cnki.cjbmb.2025.03.1514
- VernacularTitle:锌指结构转录因子锌指蛋白148和SP5对P53转录活性的作用
- Author:
Dai-Wei WANG
1
;
Chen ZHOU
;
Pin-Zheng ZHANG
;
Xu-Ying WANG
;
Jia-Wen LI
;
Yu-Kai MA
;
Jia-Qi YAN
;
Zhi-Ting WANG
;
Jia-Qi WANG
;
Zhi-Yi GUO
Author Information
1. 华北理工大学基础医学院病原生物学系,河北 唐山 063200;河北省慢性疾病基础医学重点实验室,河北 唐山 063200
- Publication Type:Journal Article
- Keywords:
zinc finger;
zinc finger protein 148(ZNF148);
specificity protein 5(SP5);
P53(tumor protein P53);
transcriptional regulation
- From:
Chinese Journal of Biochemistry and Molecular Biology
2025;41(5):707-715
- CountryChina
- Language:Chinese
-
Abstract:
P53 is a key tumor suppressor gene,which is regulated in many ways.Zinc finger 148(ZNF148)and SP5,as zinc finger transcription factors(TFs),play important roles in tumor suppression and carcinogenesis.The regulatory relationship between these two TFs and p53 has not been reported.In this paper,Ishikawa and A549 cell lines with different p53 expression levels were used as research mod-els to explore the transcriptional regulation of the P53 gene by ZNF148 and SP5.The data showed that there were differences in the expression of ZNF148 and SP5 in the two cell lines.The mRNA expression of ZNF148 in Ishikawa was 1.9 times higher than that of A549,and the mRNA expression of SP5 in A549 was 802.4 times that of ZNF148.Data showed that in Ishikawa cells,the expression of P53 de-creased(81.8％)after ZNF148 knockdown,and increased(2.6 times)after SP5 overexpression.Transfection of si-SP5 and ZNF148 expression plasmids into A549 cells increased the mRNA expression of P53 by 6.6 times and 14.6 times,respectively.These results indicate that ZNF148 could activate,whereas SP5 could inhibit,P53 expression.The conserved cis-element of ZNF148 and SP5 TFs was found in the region of the P53 promoter by bioinformatics methods.The data from dual luciferase reporter gene assay showed that the luciferase activity of ZNF148 in Ishikawa and A549 cells was increased by 2.1-fold and 4.2-fold compared with the control group(P＜0.05).Compared with the control group,the normalized relative luciferase activity of transfected SP5 decreased by 77.1％and 35.7％(P＜0.05).However,when the cis-element of ZNF148 and SP5 was mutated,the effect disappeared.Further trans-fection of ZNF148 and SP5 with different ratios revealed that SP5 could reverse the transcriptional activa-tion of P53 by ZNF148.Studies have shown that ZNF148 shares a common site with SP5,and the ratio of the two TFs may influence the transcriptional activity of P53.The expression of the Wnt pathway and the cell proliferation rate after knockdown of ZNF148 and SP5 were further studied to explore the role of the two TFs.Our data show that ZNF148 and SP5 could regulate the transcriptional activity of P53,and their expression levels and interaction may be the key factors regulating P53 expression.
