title: Identification and characterization of alternatively transcribed form of peroxiredoxin IV gene that is specifically expressed in spermatids of postpubertal mouse testis.
abstract: 2-Cysteine (Cys) peroxiredoxins (Prxs), which include mammalian Prxs I-IV, possess two conserved Cys residues that are readily oxidized by H(2)O(2) to form a disulfide. In the case of Prx I-III, the disulfide is reduced by thioredoxin, thus enabling these proteins to function as peroxidases. Prx IV was shown previously to be synthesized as a 31-kDa polypeptide with an NH(2)-terminal signal peptide that is subsequently cleaved to generate a 27-kDa form of the protein that is localized to the endoplasmic reticulum. A form of Prx IV, larger than 27 kDa revealed by immunoblot analysis was suggested to represent the unprocessed, 31-kDa form, but this larger form was detected only in spermatids of the postpubertal testis. We now show that the larger form of Prx IV (here designated Prx IV-L) detected in the testis is actually a product of alternative transcription of the Prx IV gene that is encoded by newly identified exon 1A together with exons 2-7 that are shared with the 27-kDa form (designated Prx IV-S). Prx IV-L was detected in spermatids but not in mature sperm, it could form disulfide-linked dimers but not higher order oligomers via oxidation, and it was resistant to hyperoxidation unless additional reductant was added, suggesting that its peroxidase activity is limited in vivo. Phylogenetic analysis showed that the Prx IV-S gene is present in all vertebrates examined, whereas the Prx IV-L gene was detected only in placental mammals. We suggest that Prx IV-L functions as an H(2)O(2) sensor that mediates protein thiol oxidation required for the maturation of spermatozoa in placental mammals.
authors.affiliation: Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, Korea. shyim@rics.bwh.harvard.edu
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Yim
authors.forename: Yoo-Jin
authors.initials: YJ
authors.lastname: Kim
authors.forename: Sue Young
authors.initials: SY
authors.lastname: Oh
authors.forename: Junichi
authors.initials: J
authors.lastname: Fujii
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Vadim N
authors.initials: VN
authors.lastname: Gladyshev
authors.forename: Sue Goo
authors.initials: SG
authors.lastname: Rhee
mesh_terms: D000818:Animals; D005091:Exons / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D010084:Oxidation-Reduction; D054464:Peroxiredoxins / Q000096:biosynthesis* / Q000235:genetics; D010802:Phylogeny; D012741:Sexual Maturation / Q000502:physiology*; D013087:Spermatids / Q000166:cytology / Q000201:enzymology*; D013737:Testis / Q000166:cytology / Q000201:enzymology*; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D007527:Isoenzymes; D006861:Hydrogen Peroxide; D054464:Peroxiredoxins