title: The essential role of FKBP38 in regulating phosphatase of regenerating liver 3 (PRL-3) protein stability.
abstract: The phosphatase of regenerating liver-3 (PRL-3) is a member of protein tyrosine phosphatases and whose deregulation is implicated in tumorigenesis and metastasis of many cancers. However, the underlying mechanism by which PRL-3 is regulated is not known. In this study, we identified the peptidyl prolyl cis/trans isomerase FK506-binding protein 38 (FKBP38) as an interacting protein of PRL-3 using a yeast two-hybrid system. FKBP38 specifically binds to PRL-3 in vivo, and that the N-terminal region of FKBP38 is crucial for binding with PRL-3. FKBP38 overexpression reduces endogenous PRL-3 expression levels, whereas the depletion of FKBP38 by siRNA increases the level of PRL-3 protein. Moreover, FKBP38 promotes degradation of endogenous PRL-3 protein via protein-proteasome pathway. Furthermore, FKBP38 suppresses PRL-3-mediated p53 activity and cell proliferation. These results demonstrate that FKBP38 is a novel regulator of the oncogenic protein PRL-3 abundance and that alteration in the stability of PRL-3 can have a dramatic impact on cell proliferation. Thus, FKBP38 may play a critical role in tumorigenesis.
authors.affiliation: Graduate School of Medical Science and Engineering, Biomedical Research Center, KAIST, Daejeon 305-701, Republic of Korea.
authors.forename: Myung-Suk
authors.initials: MS
authors.lastname: Choi
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Min
authors.forename: Haiyoung
authors.initials: H
authors.lastname: Jung
authors.forename: Ju Dong
authors.initials: JD
authors.lastname: Lee
authors.forename: Tae Ho
authors.initials: TH
authors.lastname: Lee
authors.forename: Heung Kyu
authors.initials: HK
authors.lastname: Lee
authors.forename: Ook-Joon
authors.initials: OJ
authors.lastname: Yoo
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D004795:Enzyme Stability; D057809:HEK293 Cells; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: C471205:FKBP8 protein, human; D009363:Neoplasm Proteins; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases; D046988:Proteasome Endopeptidase Complex; D022021:Tacrolimus Binding Proteins