title: Cloning and characterization of a novel isoform of iodotyrosine dehalogenase 1 (DEHAL1) DEHAL1C from human thyroid: comparisons with DEHAL1 and DEHAL1B.
abstract: The human iodotyrosine dehalogenase 1 (DEHAL1) gene is composed of six exons. Two isoforms (DEHAL1 and DEHAL1B) have been published in GenBank, both of which have a nitroreductase domain and arise from differential splicing in exon 5. We recently showed that the DEHAL1 isoform is a transmembrane protein that efficiently catalyzes the NADPH-dependent deiodination of mono (L-MIT) and diiodotyrosine (L-DIT) in human embryonic kidney-293 (HEK293) cells. In the present study, we establish the existence of a new transcript, DEHAL1C, in the human thyroid with a terminal exon that lacks in the DEHAL1 transcript. This exon is the complete exon 5, which is spliced in the DEHAL1B mRNA variant. These two variants encode proteins with differing C-terminal domains. Using quantitative reverse transcription polymerase chain reaction, we found that the expression of the mRNA of DEHAL1C and DEHAL1B was lower than that of DEHAL1 mRNA in the thyroid. We also observed that human DEHAL1B and DEHAL1C proteins are rapidly degraded in stably transfected HEK293 cells, unlike the DEHAL1 protein, and that exposure to the proteasome inhibitor MG132 resulted in accumulation of these proteins that was markedly time- and concentration-dependent. These findings show that the cytoplasmic tail could play a role in the stability of the protein.
authors.affiliation: FRE 2939 CNRS, Institut Gustave Roussy, Villejuif, France., Laboratoire de Pharmacologie et d'Hormonologie, ISBA, Cotonou, Benin, France.
authors.forename: Sédami
authors.initials: S
authors.lastname: Gnidehou
authors.forename: Ludovic
authors.initials: L
authors.lastname: Lacroix
authors.forename: Alphonse
authors.initials: A
authors.lastname: Sezan
authors.forename: Renée
authors.initials: R
authors.lastname: Ohayon
authors.forename: Marie-Sophie
authors.initials: MS
authors.lastname: Noël-Hudson
authors.forename: Stanislas
authors.initials: S
authors.lastname: Morand
authors.forename: Jacques
authors.initials: J
authors.lastname: Francon
authors.forename: Françoise
authors.initials: F
authors.lastname: Courtin
authors.forename: Alain
authors.initials: A
authors.lastname: Virion
authors.forename: Corinne
authors.initials: C
authors.lastname: Dupuy
mesh_terms: D017398:Alternative Splicing; D002460:Cell Line; D003001:Cloning, Molecular; D004305:Dose-Response Relationship, Drug; D005091:Exons; D006801:Humans; D006867:Hydrolases / Q000737:chemistry* / Q000235:genetics*; D007976:Leupeptins / Q000494:pharmacology; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics*; D008954:Models, Biological; D008957:Models, Genetic; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013961:Thyroid Gland / Q000378:metabolism*; D013997:Time Factors
chemical_list: D007976:Leupeptins; D008565:Membrane Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D006867:Hydrolases; C497447:IYD protein, human; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde