Toward selective CK2alpha and CK2alpha' inhibitors: Development of a novel whole-cell kinase assay by Autodisplay of catalytic CK2alpha'

Journal of Pharmaceutical and Biomedical Analysis
Andre BollackeJoachim Jose

Abstract

Human protein kinase CK2 is an emerging target for the development of novel anti-cancer therapeutics. CK2 is a tetramer composed of two catalytically active α- and/or α'-subunits, bound to a dimer of the regulatory β-subunit. Inhibitors targeting one of the two isoforms of the catalytically active CK2-subunit (α- and α') are important to study the distinct functions of these isoforms toward different CK2 associated pathologies. The present study for the first time describes the successful Autodisplay of the CK2α'-subunit, the paralogous isoform of CK2α. Expression on the cell surface of E. coli of CK2α' alone and in combination with the regulatory CK2β-subunit was confirmed by outer membrane isolation and protease accessibility test. Kinase activity of surface displayed CK2 could be detected with a CE-based assay and was found to be 3.06×10(-6) μmol/min for CK2α' alone and 1.02×10(-5) μmol/min when expressed in combination with CK2β. The comparison of the influence of NaCl on activity of the α'-subunit alone and in combination with the non-catalytically active β-subunit indicated interaction of both subunits on the cell surface. TMCB (4,5,6,7-tetrabromo-2-(dimethylamino)-1H-benzo[d]imidazol-1-yl)acetic acid), a known CK2 inhibi...Continue Reading

References

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Oct 24, 2007·Molecular and Cellular Biology·David Y LouDavid C Seldin
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Mar 2, 2012·Bioorganic & Medicinal Chemistry·Claas HundsdörferJoachim Jose
Mar 20, 2012·Journal of Biotechnology·Stephanie D SchumacherJoachim Jose
May 10, 2012·Journal of Biotechnology·Joachim JoseMark George Teese

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