Identification of the core promoter of STK11 gene and its transcriptional regulation by p53  

作　　者：Maojin Yao Yongjun Wang Hongwei Shen Wenfeng Ning Jianguang Tang Xiangping Wang Jie Li Shiquang Zhou Xin Yi Ch-enjie Li Yi Chu Fei Wang Xiaoliu Shi 

机构地区：[1]The Second Xiang Ya Hospital of Central South University, Changsha 410011, China [2]Zhu Zhou No. 1 Hospital, ZhuZhou 412000, China

出　　处：《Progress in Natural Science:Materials International》2008年第3期273-280,共8页自然科学进展·国际材料（英文版）

基　　金：supported by National Natural Science Foundation of China(Grant No.30400537).

摘　　要：Peutz-Jeghers syndrome （PJS） is an autosomal dominant disease characterized by mucocutaneous pigmentation and hamartomatous polyps. Most cases of PJS involve the inactivation of germline mutations in the serine/threonine kinase gene STK11 which is also known as LKB1. The function of STKll was previously linked to the tumor suppressor p53 and was shown to activate the p53 target p21/ WAF1. Recently, STK11 was reported to be interacting with p53 physically in the nucleus and it can directly or indirectly phosphorylate p53. Here we characterized the 5-flanking region of human STK11 gene and identified a 161-bp fragment with promoter activity. Sequence analysis, mutagenesis and gel shift studies revealed a binding site of Sp 1 and p53, which affects the promoter activity. Mutation analyses showed that this fragment was required for p53-mediated transcriptional activation. This transcriptional activation was further confirmed by real-time quantitative RT-PCR and Western blot analysis. Transient transfection of p53 expression plasmid into fetal liver cell lines increased STKll mRNA and protein levels. In conclusion, our results reveal a new role for p53 in elevating STK11 gene expression via a positive feedback pattern.Peutz-Jeghers syndrome (PJS) is an autosomal dominant disease characterized by mucocutaneous pigmentation and hamartomatous polyps. Most cases of PJS involve the inactivation of germline mutations in the serine/threonine kinase gene STK11 which is also known as LKB1. The function of STK11 was previously linked to the tumor suppressor p53 and was shown to activate the p53 target p21/ WAF1. Recently, STK11 was reported to be interacting with p53 physically in the nucleus and it can directly or indirectly phosphorylate p53. Here we characterized the 50-flanking region of human STK11 gene and identified a 161-bp fragment with promoter activity. Sequence analysis, mutagenesis and gel shift studies revealed a binding site of Sp1 and p53, which affects the promoter activity. Mutation analyses showed that this fragment was required for p53-mediated transcriptional activation. This transcriptional activation was further confirmed by real-time quantitative RT-PCR and Western blot analysis. Transient transfection of p53 expression plasmid into fetal liver cell lines increased STK11 mRNA and protein levels. In conclusion, our results reveal a new role for p53 in elevating STK11 gene expres- sion via a positive feedback pattern.

关 键 词：Peutz-Jeghers syndrome STK11 P53 Promoter transcriptional regulation Tumor suppressor 

分 类 号：R394[医药卫生—医学遗传学]