title: Evolution of Na,K-ATPase beta m-subunit into a coregulator of transcription in placental mammals.
abstract: Change in gene functions (gene cooption) is one of the key mechanisms of molecular evolution. Genes can acquire new functions via alteration in properties of encoded proteins and/or via changes in temporal or spatial regulation of expression. Here we demonstrate radical changes in the functions of orthologous ATP1B4 genes during evolution of vertebrates. Expression of ATP1B4 genes is brain-specific in teleost fishes, whereas it is predominantly muscle-specific in tetrapods. The encoded beta m-proteins in fish, amphibian, and avian species are beta-subunits of Na,K-ATPase located in the plasma membrane. In placental mammals beta m-proteins lost their ancestral functions, accumulate in nuclear membrane of perinatal myocytes, and associate with transcriptional coregulator Ski-interacting protein (SKIP). Through interaction with SKIP, eutherian beta m acquired new functions as exemplified by regulation of TGF-beta-responsive reporters and by augmentation of mRNA levels of Smad7, an inhibitor of TGF-beta signaling. Thus, orthologous vertebrate ATP1B4 genes represent an instance of gene cooption that created fundamental changes in the functional properties of the encoded proteins.
authors.affiliation: Department of Physiology and Pharmacology, University of Toledo College of Medicine, 3000 Arlington Avenue, Toledo, OH 43614, USA.
authors.forename: Nikolay B
authors.initials: NB
authors.lastname: Pestov
authors.forename: Nisar
authors.initials: N
authors.lastname: Ahmad
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Korneenko
authors.forename: Hao
authors.initials: H
authors.lastname: Zhao
authors.forename: Rossen
authors.initials: R
authors.lastname: Radkov
authors.forename: Danièle
authors.initials: D
authors.lastname: Schaer
authors.forename: Sophie
authors.initials: S
authors.lastname: Roy
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Bibert
authors.forename: Käthi
authors.initials: K
authors.lastname: Geering
authors.forename: Nikolai N
authors.initials: NN
authors.lastname: Modyanov
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002642:Chick Embryo; D002645:Chickens; D019143:Evolution, Molecular; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D009687:Nuclear Proteins / Q000502:physiology; D021122:Protein Subunits / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D023721:Tetraodontiformes; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D014982:Xenopus laevis
chemical_list: D009687:Nuclear Proteins; D021122:Protein Subunits; C491762:Skiip protein, mouse; D014157:Transcription Factors; D000254:Sodium-Potassium-Exchanging ATPase