title: A metabolic enzyme of the short-chain dehydrogenase/reductase superfamily may moonlight in the nucleus as a repressor of promoter activity.
abstract: Transcriptional repression often depends on the action of recruited co-repressor complexes with intrinsic enzymatic activities. The composition of these complexes depends on the nicotine amide dinucleotide co-factors and is thus directly reflective of the metabolic state of the cells. This study provides evidence that an enzyme, hRoDH-E2, with cytoplasmic phosphorylated and reduced forms of NAD-dependent retinol dehydrogenase activity may function in the nucleus as a transcriptional repressor. By using the promoter of the epidermal late differentiation marker profilaggrin as a model, we show that both in vivo and in vitro the protein is recruited over the promoter. hRoDH-E2 represses profilaggrin promoter activity by altering the function of other activators, such as Sp1. The repressive function is associated with the ability of nuclear hRoDH-E2 to modulate the acetylation/deacetylation activity in the vicinity of transcription initiation site. These findings add hRoDH-E2 to the small group of metabolic enzymes, which, by being recruited over promoter regions, could directly link the cytoplasmic and nuclear functions within the cell.
authors.affiliation: Living Skin Bank, Department of Oral Biology and Pathology, School of Dental Medicine, SUNY Stony Brook, New York 11794, USA. nmarkova@notes.cc.sunysb.edu
authors.forename: Nelli G
authors.initials: NG
authors.lastname: Markova
authors.forename: Adriana
authors.initials: A
authors.lastname: Pinkas-Sarafova
authors.forename: Marcia
authors.initials: M
authors.lastname: Simon
mesh_terms: D000107:Acetylation; D000429:Alcohol Oxidoreductases / Q000235:genetics* / Q000378:metabolism*; D001483:Base Sequence; D002467:Cell Nucleus / Q000201:enzymology; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D000078404:Epidermal Cells; D000091344:Filaggrin Proteins; D020868:Gene Silencing / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics; D015603:Keratinocytes / Q000166:cytology / Q000201:enzymology*; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D002843:Chromatin; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D012097:Repressor Proteins; D016329:Sp1 Transcription Factor; D000429:Alcohol Oxidoreductases; C022520:retinol dehydrogenase