title: HuR represses Wnt/β-catenin-mediated transcriptional activity by promoting cytoplasmic localization of β-catenin.
abstract: β-Catenin is the key transcriptional activator of canonical Wnt signaling in the nucleus; thus, nuclear accumulation of β-catenin is a critical step for expressing target genes. β-Catenin accumulates in the nucleus of cancer cells where it activates oncogenic target genes. Hu antigen R (HuR) is a RNA binding protein that regulates multiple post-transcriptional processes including RNA stability. Thus, cytoplasmic HuR protein may be involved in tumorigenesis by stabilizing oncogenic transcripts, but the molecular mechanism remains unclear. Here, we observed that Wnt/β-catenin signaling induced export of the HuR protein, whereas HuR overexpression promoted accumulation of the β-catenin protein in the cytoplasm. Thus, Wnt/β-catenin-mediated transcriptional activity in the nucleus was reduced by overexpressing HuR. These results suggest novel and uncharacterized cytoplasmic β-catenin functions related to HuR-mediated RNA metabolism in cancer cells.
authors.affiliation: Department of Molecular Biology, Dankook University, Yongin, Gyeonggi-do 448-701, Republic of Korea.
authors.forename: Inae
authors.initials: I
authors.lastname: Kim
authors.affiliation: Department of Molecular Biology, Dankook University, Yongin, Gyeonggi-do 448-701, Republic of Korea.
authors.forename: Jung
authors.initials: J
authors.lastname: Hur
authors.affiliation: Department of Molecular Biology, Dankook University, Yongin, Gyeonggi-do 448-701, Republic of Korea. Electronic address: sjsj@dankook.ac.kr.
authors.forename: Sunjoo
authors.initials: S
authors.lastname: Jeong
mesh_terms: D002460:Cell Line; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism*; D051959:ELAV Proteins / Q000378:metabolism*; D000067780:ELAV-Like Protein 1; D006801:Humans; D018021:Lithium Chloride / Q000494:pharmacology; D008954:Models, Biological; D055550:Protein Stability / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D051820:TCF Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects; D060449:Wnt Signaling Pathway / Q000187:drug effects; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D051820:TCF Transcription Factors; D051176:beta Catenin; D018021:Lithium Chloride
keywords: Cytoplasmic β-catenin; HuR; Transcriptional activity; Wnt/β-catenin