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Protein kinase CK2 is necessary for the adipogenic differentiation of human mesenchymal stem cells

 
: Schwind, L.; Wilhelm, N.; Kartarius, S.; Montenarh, M.; Gorjup, E.; Götz, C.

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Biochimica et biophysica acta 1853 (2015), Nr.10, S.2207-2216
ISSN: 0006-3002
ISSN: 0167-4889
Englisch
Zeitschriftenaufsatz
Fraunhofer IBMT ()

Abstract
CK2 is a serine/threonine protein kinase, which is so important for many aspects of cellular regulation that life without CK2 is impossible. Here, we analysed CK2 during adipogenic differentiation of human mesenchymal stem cells (hMSCs). With progress of the differentiation CK2 protein level and the kinase activity decreased. Whereas CK2 alpha remained in the nucleus during differentiation, the localization of CK2 beta showed a dynamic shuttling in the course of differentiation. Over the last years a large number of inhibitors of CK2 kinase activity were generated with the idea to use them in cancer therapy. Our results show that two highly specific inhibitors of CK2, CX-4945 and quinalizarin, reduced its kinase activity in proliferating hMSC with a similar efficiency. CK2 inhibition by quinalizarin resulted in nearly complete inhibition of differentiation whereas, in the presence of CX-4945, differentiation proceeded similar to the controls. In this case, differentiation was accompanied by the loss of CX-4945 inhibitory function. By analysing the subcellular localization of PPAR gamma 2, we found a shift from a nuclear localization at the beginning of differentiation to a more cytoplasmic localization in the presence of quinalizarin. Our data further show for the first time that a certain level of CK2 kinase activity is required for adipogenic stem cell differentiation and that inhibition of CK2 resulted in an altered localization of PPAR gamma 2, an early regulator of differentiation.

: http://publica.fraunhofer.de/dokumente/N-369475.html