title: Transcription factor AP-2β suppresses cervical cancer cell proliferation by promoting the degradation of its interaction partner β-catenin.
abstract: Transcription factor AP-2β mediates the transcription of a number of genes implicated in mammalian development, cell proliferation, and carcinogenesis. Although the expression pattern of AP-2β has been analyzed in cervical cancer cell lines, the functions and molecular mechanism of AP-2β are unknown. Here, we found that AP-2β significantly inhibits TCF/LEF reporter activity. Moreover, AP-2β and β-catenin interact both in vitro through GST pull-down assays and in vivo by co-immunoprecipitation. We further identified the interaction regions to the DNA-binding domain of AP-2β and the 1-9 Armadillo repeats of β-catenin. Moreover, AP-2β binds with β-TrCP and promotes the degradation of endogenous β-catenin via the proteasomal degradation pathway. Immunohistochemistry analysis revealed a negative correlation between the two proteins in cervical cancer tissues and cell lines. Finally, functional analysis showed that AP-2β suppresses cervical cancer cell growth in vitro and in vivo by inhibiting the expression of Wnt downstream genes. Taken together, these findings demonstrated that AP-2β functions as a novel inhibitor of the Wnt/β-catenin signaling pathway in cervical cancer.
authors.affiliation: Key Laboratory of Protein Chemistry and Development Biology of State Education Ministry of China, College of Life Science, Changsha, Hunan, China.
authors.forename: Fangmei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Key Laboratory of Protein Chemistry and Development Biology of State Education Ministry of China, College of Life Science, Changsha, Hunan, China.
authors.forename: Wenhuan
authors.initials: W
authors.lastname: Huang
authors.affiliation: Key Laboratory of Protein Chemistry and Development Biology of State Education Ministry of China, College of Life Science, Changsha, Hunan, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Hu
authors.affiliation: Key Laboratory of Protein Chemistry and Development Biology of State Education Ministry of China, College of Life Science, Changsha, Hunan, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Chen
authors.affiliation: Key Laboratory of Protein Chemistry and Development Biology of State Education Ministry of China, College of Life Science, Changsha, Hunan, China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Protein Chemistry and Development Biology of State Education Ministry of China, College of Life Science, Changsha, Hunan, China.
authors.forename: Junlu
authors.initials: J
authors.lastname: Qiu
authors.affiliation: Key Laboratory of Protein Chemistry and Development Biology of State Education Ministry of China, College of Life Science, Changsha, Hunan, China.
authors.forename: Zhongheng
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Reproductive Medicine Center, Changsha Hospital for Maternal & Child Health Care, Changsha, Hunan, China.
authors.forename: Jianmei
authors.initials: J
authors.lastname: Zhang
authors.affiliation: College of Engineering and Design, Hunan Normal University, Changsha, Hunan, China.
authors.forename: Limin
authors.initials: L
authors.lastname: Li
authors.affiliation: Xiangya Second Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Protein Chemistry and Development Biology of State Education Ministry of China, College of Life Science, Changsha, Hunan, China.
authors.forename: Xiaofeng
authors.identifier: 0000-0002-6163-3915
authors.initials: X
authors.lastname: Ding
authors.affiliation: Key Laboratory of Protein Chemistry and Development Biology of State Education Ministry of China, College of Life Science, Changsha, Hunan, China.
authors.forename: Shuanglin
authors.initials: S
authors.lastname: Xiang
authors.affiliation: Key Laboratory of Protein Chemistry and Development Biology of State Education Ministry of China, College of Life Science, Changsha, Hunan, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D002584:Cervix Uteri / Q000378:metabolism / Q000473:pathology*; D005260:Female; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D060066:Protein Interaction Maps; D059748:Proteolysis; D050656:Transcription Factor AP-2 / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D050656:Transcription Factor AP-2; D051176:beta Catenin; D046988:Proteasome Endopeptidase Complex
keywords: AP-2β; cervical cancer; β-catenin