title: Novel p53 target gene FUCA1 encodes a fucosidase and regulates growth and survival of cancer cells.
abstract: The tumor suppressor p53 functions by inducing the transcription of a collection of target genes. We previously attempted to identify p53 target genes by microarray expression and ChIP-sequencing analyses. In this study, we describe a novel p53 target gene, FUCA1, which encodes a fucosidase. Although fucosidase, α-l-1 (FUCA1) has been reported to be a lysosomal protein, we detected it outside of lysosomes and observed that its activity is highest at physiological pH. As there is a reported association between fucosylation and tumorigenesis, we investigated the potential role of FUCA1 in cancer. We found that overexpression of FUCA1, but not a mutant defective in enzyme activity, suppressed the growth of cancer cells and induced cell death. Furthermore, we showed that FUCA1 reduced fucosylation and activation of epidermal growth factor receptor, and concomitantly suppressed epidermal growth factor signaling pathways. FUCA1 loss-of-function mutations are found in several cancers, its expression is reduced in cancers of the large intestine, and low FUCA1 expression is associated with poorer prognosis in several cancers. These results show that protein defucosylation mediated by FUCA1 is involved in tumor suppression.
authors.affiliation: Division of Rare Cancer Research, National Cancer Center Research Institute, Tokyo, Japan.|Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.
authors.forename: Issei
authors.initials: I
authors.lastname: Ezawa
authors.affiliation: Radiobiology Division, National Cancer Center Research Institute, Tokyo, Japan.|Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Tokyo, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Sawai
authors.affiliation: Radiobiology Division, National Cancer Center Research Institute, Tokyo, Japan.|Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Tokyo, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kawase
authors.affiliation: Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.|Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Okabe
authors.affiliation: Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Tsutsumi
authors.affiliation: Department of Clinical Genomics, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ichikawa
authors.affiliation: J-Oil Mills, Inc., Yokohama, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Tokyo, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Tashiro
authors.affiliation: Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Namiki
authors.affiliation: Division of Rare Cancer Research, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kondo
authors.affiliation: Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Semba
authors.affiliation: Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.affiliation: Radiobiology Division, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Taya
authors.affiliation: Division of Cancer Development System, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nakagama
authors.affiliation: Division of Rare Cancer Research, National Cancer Center Research Institute, Tokyo, Japan.|Radiobiology Division, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Rieko
authors.initials: R
authors.lastname: Ohki
mesh_terms: D016923:Cell Death; D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005643:Fucose / Q000378:metabolism; D006801:Humans; D050505:Mutant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D005644:alpha-L-Fucosidase / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*
chemical_list: D050505:Mutant Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D005643:Fucose; D004815:Epidermal Growth Factor; C512478:EGFR protein, human; D066246:ErbB Receptors; D005644:alpha-L-Fucosidase
keywords: EGFR; FUCA1; fucosidase; fucosylation; p53