title: NEDD4 controls the expression of GUCD1, a protein upregulated in proliferating liver cells.
abstract: Liver regeneration is a unique means of studying cell proliferation in vivo. Screening of a large cDNA library from regenerating liver has previously allowed us to identify and characterize a cluster of genes encoding proteins with important roles in proliferative processes. Here, by examining different rat and human tissues as well as cell lines, we characterized a highly conserved gene, guanylyl cyclase domain containing 1 (GUCD1), whose modulation occurs in liver regeneration and cell cycle progression in vitro. High-level expression of GUCD1 transcripts was observed in livers from patients with hepatocellular carcinoma. A yeast two-hybrid interaction assay, aimed at identifying any relevant interaction partners of GUCD1, revealed direct interactions with NEDD4-1 (E3 ubiquitin protein ligase neural precursor cell expressed, developmentally downregulated gene 4), resulting in control of GUCD1 stability. Thus, we have characterized expression and function of a ubiquitous protein, GUCD1, which might have a role in regulating normal and abnormal cell growth in the liver.
authors.affiliation: Department of Experimental Medicine; University of Perugia; Perugia, Italy.
authors.forename: Marina Maria
authors.initials: MM
authors.lastname: Bellet
authors.affiliation: Department of Experimental Medicine; University of Perugia; Perugia, Italy.
authors.forename: Danilo
authors.initials: D
authors.lastname: Piobbico
authors.affiliation: Department of Experimental Medicine; University of Perugia; Perugia, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Bartoli
authors.affiliation: Department of Experimental Medicine; University of Perugia; Perugia, Italy.
authors.forename: Marilena
authors.initials: M
authors.lastname: Castelli
authors.affiliation: Department of Experimental Medicine; University of Perugia; Perugia, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Pieroni
authors.affiliation: Department of Experimental Medicine; University of Perugia; Perugia, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Brunacci
authors.affiliation: Department of Experimental Medicine; University of Perugia; Perugia, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Chiacchiaretta
authors.affiliation: Department of Experimental Medicine; University of Perugia; Perugia, Italy.
authors.forename: Rachele
authors.initials: R
authors.lastname: Del Sordo
authors.affiliation: Department of Experimental Medicine; University of Perugia; Perugia, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Fallarino
authors.affiliation: Department of Experimental Medicine; University of Perugia; Perugia, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Sidoni
authors.affiliation: Department of Experimental Medicine; University of Perugia; Perugia, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Puccetti
authors.affiliation: Department of Experimental Medicine; University of Perugia; Perugia, Italy.
authors.forename: Luigina
authors.initials: L
authors.lastname: Romani
authors.affiliation: Department of Experimental Medicine; University of Perugia; Perugia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Servillo
authors.affiliation: Department of Experimental Medicine; University of Perugia; Perugia, Italy.
authors.forename: Maria Agnese
authors.initials: MA
authors.lastname: Della Fazia
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle; D049109:Cell Proliferation; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D008115:Liver Regeneration / Q000235:genetics*; D051379:Mice; D000075702:Nedd4 Ubiquitin Protein Ligases; D017207:Rats, Sprague-Dawley; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; C000618479:NEDD4L protein, rat; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618483:Nedd4 protein, human; C000618484:Nedd4 protein, rat; C000618461:Nedd4l protein, mouse; D044767:Ubiquitin-Protein Ligases; C000594563:GUCD1 protein, human; D006162:Guanylate Cyclase
keywords: HCC; liver regeneration; partial hepatectomy; proliferation; ubiquitination
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