Authors: Iria BarciaSanjurjo Marta VázquezCedeira Ramiro Barcia Pedro A Lazo
Publish Date: 2013/03/13
Volume: 18, Issue: 4, Pages: 473-482
Abstract
The human vacciniarelated kinase VRK proteins VRK1 and VRK2 regulate different processes such as the cell cycle DNA damage response and signaling by mitogenactivated protein kinases in response to growth factors or cellular stress Alterations in expression levels of these Ser–Thr kinases are associated with cancer and neurodegenerative diseases These functions suggest that they might also be targets of toxic metals and thus contribute to the pathogenic effects associated with metal intoxication VRK1 is inhibited by cadmium copper and mercury and VRK2 is more sensitive to cadmium and much less sensitive to copper and mercury Both kinases are insensitive to lead and cobalt VRK1 is in general more sensitive than VRK2 in the low micromolar range This inhibitory effect induced by these metals was detected in an autophosphorylation assay as well as in phosphorylation assays using p53 and histone H3 as substrates The accumulation of these three metals in cells can contribute by inhibition of VRKs to their toxic pathogenic effects particularly their neurological manifestations In this context copper has not generally been associated with any intoxication syndrome except Wilson’s syndrome but it might be implicated in some alterations with which it has not yet been associatedIBS and MVC have fellowships from Universidad de Santiago and JAE/CSIC/Fondo Social Europeo respectively This work was funded by grants from Ministerio de Educación Ciencia e Innovación SAF201014935 Junta de Castilla y León CSI006A112 and KutxaFundación INBIOMED to PAL and from Xunta de Galicia to R B
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