Retinoids inhibit human epidermal keratinocyte RNase P activity.
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.
Papadimou
Evangelia
E
Department of Biochemistry, University of Patras, GR-26500 Patras, Greece.
Pavlidou
Despina
D
Séraphin
Bertrand
B
Tsambaos
Dionysios
D
Drainas
Denis
D
D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015603:Keratinocytes / Q000201:enzymology*; D007700:Kinetics; D012176:Retinoids / Q000737:chemistry / Q000494:pharmacology*; D043262:Ribonuclease P / Q000037:antagonists & inhibitors*
D012176:Retinoids; D043262:Ribonuclease P