title: PRL-3 activates NF-κB signaling pathway by interacting with RAP1.
abstract: Phosphatase of regenerating liver (PRL-3) promotes cancer metastasis through enhanced cell motility and invasiveness, however its role in tumorigenesis remains unclear. Herein, we reported that PRL-3 interacts with telomere-related protein RAP1. PRL-3 promotes the cytosolic localization of RAP1, which is counteracted by silencing of PRL-3. Immunohistochemical staining of colon cancer tissue array (n=170) revealed that high level of PRL-3 associates with cytosolic localization of RAP1 (p=0.01). Microarray analysis showed that PRL-3 regulates expression of diverse genes and enhances phosphorylation of p65 subunit of NF-κB in a RAP1-dependent manner. Furthermore, PRL-3 transcriptionally activates RAP1 expression, which is counteracted by ablating p65. Therefore, our results demonstrate PRL-3 as a novel regulator of NF-κB signaling pathway through RAP1.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Shenyi
authors.initials: S
authors.lastname: Lian
authors.forename: Lin
authors.initials: L
authors.lastname: Meng
authors.forename: Caiyun
authors.initials: C
authors.lastname: Liu
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Xing
authors.forename: Qian
authors.initials: Q
authors.lastname: Song
authors.forename: Bin
authors.initials: B
authors.lastname: Dong
authors.forename: Yong
authors.initials: Y
authors.lastname: Han
authors.forename: Yongyong
authors.initials: Y
authors.lastname: Yang
authors.forename: Lirong
authors.initials: L
authors.lastname: Peng
authors.forename: Like
authors.initials: L
authors.lastname: Qu
authors.forename: Chengchao
authors.initials: C
authors.lastname: Shou
mesh_terms: D045744:Cell Line, Tumor; D003600:Cytosol / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D000089804:Shelterin Complex; D015398:Signal Transduction; D034501:Telomere-Binding Proteins / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D009363:Neoplasm Proteins; D000089804:Shelterin Complex; C440809:TERF2IP protein, human; D034501:Telomere-Binding Proteins; D051996:Transcription Factor RelA; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases