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Characterization of VRKl and Atxnl interaction and its functional implications

AutorMartín-Doncel, Elena ; Cantarero, Lara ; Lazo, Pedro A.
Fecha de publicación2016
EditorSociedad Española de Bioquímica y Biología Molecular
CitaciónXXXIX Congreso SEBBM (2016)
ResumenAtxn1 is the protein involved in the inherited neurodegenerative disease SCA1, an autosomal dominant disorder caused by the expansion of a triplet CAG, encoding a polyglutarnine tract (polyQ) which confers toxic properties to the protein. Nevertheless, polyQ is necessary but not sufficient to cause pathology. Indeed, is also important the nuclear localization signal, the AXH domain and a serine 776 residue. VRK1 is a Ser-Thr kinase associated with multiple processes, including the regulation ofcell cycle progression, chromatin remodeling or Cajal Bodies dynamics. Also VRK1 is mutated in neurodegenerative diseases. Previously we identified Atxnl like a potential target for VRK1, through the use of linear peptide chips. Our aim is to characterize the interaction VRKl-Atxnl and its potential functional implication. Through immunoprecipitation and nuclei isolation assays, we detected an interaction between both proteins. Besides, by HPLC fractionation is proved that Atxn1 and VRK1 elute in the same high molecular size fractions. By immunofluorescence, we did not detect any colocalization, which may indicate a transient interaction between both proteins. In a kinase assay, we observed distinct phosphorylation levels between Arxn1 with a physiological polyQ and the protein with an expanded polyQ. Only wild-type Atxn1 can be phosphorylated by VRK1. Atxn1 is degraded via ubiquitin proteasome system. Here, we showed that different mutants of Atxn1 have a similar protein accumulation in the nuclear inclusions when proteasome is inhibited with MG-132. Yet, we have evidence that VRK1 downregulation enhances the degradation of Atxn1. We believe other proteins, Iike VCP, which colocalized with Atxn1 nuclear inclusions with expanded polyQ, might be involved in this process.
DescripciónResumen del póster presentado al XXXIX Congreso de la Sociedad Española de Bioquímica y Biología Molecular, celebrado en Salamanca del 5 al 8 de septiembre de 2016.
URIhttp://hdl.handle.net/10261/169468
Aparece en las colecciones: (IBMCC) Comunicaciones congresos
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