TAILIEUCHUNG - Báo cáo khoa học: The subcellular localization of vaccinia-related kinase-2 (VRK2) isoforms determines their different effect on p53 stability in tumour cell lines

VRK is a new kinase family of unknown function. Endogenous human vacinia-related kinase 2 (VRK2) protein is present in both the nucleus and the cytosol, which is a consequence of alternative splicing of two VRK2 messages coding for proteins of 508 and 397 amino acids, respectively. | ềFEBS Journal The subcellular localization of vaccinia-related kinase-2 VRK2 isoforms determines their different effect on p53 stability in tumour cell lines Sandra Blanco Lucia Klimcakova Francisco M. Vega and Pedro A. Lazo Institute de Biologia Molecular y Celular delCancer Consejo Superior de Investigaciones Cientificas CSIC Universidad de Salamanca Spain Keywords p53 phosphorylation Ser-Thr kinase VRK2 Correspondence P. A. Lazo IBMCC-Centro de Investigacion delCancer CSIC-Universidad de Salamanca Campus Miguelde Unamuno E-37007 Salamanca Spain Fax 34 923 294 795 Tel 34 923 294 804 E-mail plazozbi@ Database Sequence VRK2B has been submitted to the GenBank database under the accession number AJ512204. Received 30 January 2006 revised 29 March 2006 accepted 31 March 2006 doi VRK is a new kinase family of unknown function. Endogenous human vacinia-related kinase 2 VRK2 protein is present in both the nucleus and the cytosol which is a consequence of alternative splicing of two VRK2 messages coding for proteins of 508 and 397 amino acids respectively. VRK2A has a C-terminal hydrophobic region that anchors the protein to membranes in the endoplasmic reticulum ER and mitochondria and it colocalizes with calreticulin calnexin and mitotracker whereas VRK2B is detected in both the cytoplasm and the nucleus. VRK2A is expressed in all cell types whereas VRK2B is expressed in cell lines in which VRK1 is cytoplasmic. Both VRK2 isoforms have an identical catalytic N-terminal domain and phosphorylate p53 in vitro uniquely in Thr18. Phosphorylation of the p53 protein in response to cellular stresses results in its stabilization by modulating its binding to other proteins. However p53 phosphorylation also occurs in the absence of stress. Only overexpression of the nuclear VRK2B isoform induces p53 stabilization by post-translational modification largely due to Thr18 phosphorylation. VRK2B may play a role in controlling the binding .

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