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A metabolic enzyme of the short-chain dehydrogenase/reductase superfamily may moonlight in the nucleus as a repressor of promoter activity.

Markova N.G., Pinkas-Sarafova A., Simon M.

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.

J. Invest. Dermatol. 126:2019-2031(2006) [PubMed] [Europe PMC]