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, CK2alpha and CK2alpha', have been reported to have distinct tissue-dependent subcellular distributions. We recently described a third isoform of the catalytic subunit, designated CK2alpha", which is highly expressed in liver. Immunoblot analysis of HuH-7 human hepatoma cell fractions as well as immunofluorescent microscopy revealed that CK2alpha" was exclusively localized to the nucleus and preferentially associated with the nuclear matrix. CK2alpha and CK2alpha' were found in nuclear, membrane, and cytosolic compartments. Deletion of the carboxy-terminal 32 amino acids from the CK2alpha" 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 CK2alpha" nuclear localization is dependent on the secondary structure of the holoenzyme directed by the carboxy-terminal sequence.
Hilgard
Philip
P
Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Huang
Tianmin
T
Wolkoff
Allan W
AW
Stockert
Richard J
RJ
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D020087:Alu Elements / Q000235:genetics*; D000595:Amino Acid Sequence / Q000235:genetics; D047390:Casein Kinase II; D002384:Catalysis; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D008969:Molecular Sequence Data; D015530:Nuclear Matrix / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics; D014176:Protein Biosynthesis / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism*; D017433:Protein Structure, Secondary; D015398:Signal Transduction / Q000502:physiology; D013347:Subcellular Fractions / Q000378:metabolism; D014018:Tissue Distribution
D010446:Peptide Fragments; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases