title: Identification of proteins suppressing the functions of oncogenic phosphatase of regenerating liver 1 and 3.
abstract: The phosphatase of regenerating liver (PRL) family, including PRL-1, PRL-2, and PRL-3, comprises protein tyrosine phosphatases whose deregulation is associated with the tumorigenesis and metastasis of many types of cancer. However, the underlying mechanism is poorly understood. In this study, aiming to increase understanding of the molecular mechanisms underlying the functions of PRL-1 and PRL-3, a yeast two-hybrid system was employed to screen for their interacting proteins. Alignment with the NCBI BLAST database revealed 12 interactive proteins: Synaptic nuclear envelope protein 2, emerin, mannose 6-phosphate receptor-binding protein 1, low-density lipoprotein receptor-related protein 10, Rab acceptor 1, tumor protein D52-like 2, selectin P ligand (SELPLG), guanylate binding protein 1, transmembrane and ubiquitin-like domain-containing 2, NADH:ubiquinone oxidoreductase subunit B8, syndecan 4 and FK506-binding protein 8 (FKBP8). These proteins are associated with cell proliferation, apoptosis, immune response, cell fate specification and metabolic process in biological process categories, and involved in various signaling pathways, including Alzheimer's disease, Parkinson's disease, Huntington's disease, hypertrophic cardiomyopathy and cell adhesion molecules. Interactions of PRL-1 with the prey proteins SELPLG and FKBP8 were confirmed by immunoprecipitation or immunostaining. Furthermore, SELPLG and FKBP8 suppressed PRL-1- or PRL-3-mediated p53 activity. Identification of the proteins interacting with PRL family proteins may provide valuable information to better understand the mechanism of PRL-mediated signal transduction in cancer and other diverse diseases.
authors.affiliation: Graduate School of Medical Science and Engineering, Biomedical Research Center, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Republic of Korea.
authors.forename: Ju-Dong
authors.initials: JD
authors.lastname: Lee
authors.affiliation: Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.
authors.forename: Haiyoung
authors.initials: H
authors.lastname: Jung
authors.affiliation: New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 701-310, Republic of Korea.
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Min
keywords: EMD; FKBP8; GBP1; LRP10; NDUFB8; PLIN3; RABAC1; SDC4; SELPLG; SYNE2; TMUB2; TPD52L2; phosphatase of regenerating liver 1; phosphatase of regenerating liver 3; screening; yeast two-hybrid