Retinoids Inhibit Human EpidermalKeratinocyte RNase P Activity

• Published in: Biological chemistry Vol. 384; no. 3; pp. 457 - 462
• Main Authors: Papadimou, E., Pavlidou, D., Séraphin, B., Tsambaos, D., Drainas, D.
• Format: Journal Article
• Language: English
• Published: Walter de Gruyter 14.03.2003
• ISSN: 1431-6730
• DOI: 10.1515/BC.2003.051

Ribonuclease P (RNase P) is a ubiquitous and essential enzyme that endonucleolytically cleaves all tRNA precursors to produce the mature 5'-end. We have investigated the effect of synthetic rertinoids (all-trans retinoic acid, acitretin) and arotinoids (Ro 13-7410, Ro 15-0778, Ro, 13-6298 and Ro 15-1570) on RNase P activity isolated for the first time from normal human epidermal keratinocytes (NHEK). All tested compounds but one (Ro 15-1570) revealed a dose-dependent inhibition of RNase P activity, indicating that they may have a direct effect on tRNA biogenesis. Detailed kinetic analysis showed that all retinoids behave as classic competitive inhibitors. On the basis of the Ki values Ro 13-7410 was found to be the strongest inhibitor among all compounds tested.