Translated Alu sequence determines nuclear localization of a novel catalytic subunit of casein kinase 2

Casein kinase 2 (CK2) is a tetrameric enzyme constitutively expressed in all eukaryotic tissues. The two known isoforms of the catalytic subunit, CK2α and CK2α′, have been reported to have distinct tissue-dependent subcellular distributions. We recently described a third isoform of the catalytic subunit, designated CK2α″, which is highly expressed in liver. Immunoblot analysis of HuH-7 human hepatoma cell fractions as well as immunofluorescent microscopy revealed that CK2α″ was exclusively localized to the nucleus and preferentially associated with the nuclear matrix. CK2α and CK2α′ were found in nuclear, membrane, and cytosolic compartments. Deletion of the carboxy-terminal 32 amino acids from the CK2α″ sequence resulted in release of the truncated green fluorescent protein fusion protein from the nuclear matrix and redistribution to both the nucleus and the cytoplasm. Demonstration that the carboxy terminus is necessary but not sufficient for nuclear retention indicates that the underlying mechanism of CK2α″ nuclear localization is dependent on the secondary structure of the holoenzyme directed by the carboxy-terminal sequence.