title: PinX1, a novel target gene of p53, is suppressed by HPV16 E6 in cervical cancer cells.
abstract: The aberrant activation of telomerase is critical for the initiation and development of human cervical cancer, which is dependent on the activation of human telomerase reverse transcriptase (hTERT). Recently, Pin2/TRF1-interacting protein X1 (PinX1) has been identified as a suppressor of hTERT. It has been found that the telomerase is activated while the level of PinX1 is decreased in cervical cancer. However, the regulatory mechanism of PinX1 in cervical cancer cells remains unclear. In the present study, we demonstrated that the level of PinX1 is regulated by p53, and p53 functions as a transcriptional factor to directly activate the expression of PinX1 in cervical cancer cells. Moreover, we found that HPV16 E6 suppresses the expression of PinX1 via inhibiting p53 transcriptional activity, resulting in the enhancement of telomerase activity. This study not only for the first time shows that PinX1 is a novel target gene of p53 but also suggests that suppression of p53/PinX1 pathway may be a novel mechanism by which HPV16 E6 enhances the telomerase activity in cervical cancer cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, Third Military Medical University, Chongqing 400038, China.
authors.forename: Gengze
authors.initials: G
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Biology, Third Military Medical University, Chongqing 400038, China.
authors.forename: Dongbo
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department 1 of clinical laboratory, No. 324 Hospital of PLA, Chongqing 400020, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Jiang
authors.affiliation: Department of Biochemistry and Molecular Biology, Third Military Medical University, Chongqing 400038, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Department of Biochemistry and Molecular Biology, Third Military Medical University, Chongqing 400038, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhou
authors.affiliation: Department of Biochemistry and Molecular Biology, Third Military Medical University, Chongqing 400038, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhong
authors.affiliation: Department of Biochemistry and Molecular Biology, Third Military Medical University, Chongqing 400038, China.
authors.forename: Min
authors.initials: M
authors.lastname: Gao
authors.affiliation: Department of Biochemistry and Molecular Biology, Third Military Medical University, Chongqing 400038, China. Electronic address: hefengtian06@aliyun.com.
authors.forename: Fengtian
authors.initials: F
authors.lastname: He
authors.affiliation: Department of Obstetrics and Gynecology, Daping Hospital, Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China. Electronic address: zhengyingru65@tom.com.
authors.forename: Yingru
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D015153:Blotting, Western; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009154:Mutation; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D034622:RNA Interference; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D018797:Cell Cycle Proteins; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; C440808:PINX1 protein, human; D012097:Repressor Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D019098:Telomerase
keywords: Cervical cancer; HPV16 E6; PinX1; Telomerase; p53