Regulatory role of CK2 during the progression of cell cycle.
The protein kinase casein kinase 2 (CK2) is a ubiquitous eukaryotic serine/threonine protein kinase that plays an important role in cell cycle progression. We find that (1) CK2 interacts with a tumor suppressor protein, adenomatous polyposis coli (APC) that occurs at the highest level in G2/M, and (2) the C-terminal region of APC, between amino acid residues 2086-2394, has the strongest activity to suppress CK2. Over-expression of this fragment in HEK293 cells or colorectal carcinoma cells that have truncated mutant APC proteins down-regulates cell proliferation rates as well as colony formation on soft agar. These results indicate that the complex formation between CK2 and full-length APC regulates CK2 activity that, in turn, regulates cell cycle progression, whereas truncated APC in colorectal carcinomas are unable to regulate the cell cycle. In the process to look for the downstream target for CK2, we found that eukaryotic translation initiation factor 5 (eIF5) is phosphorylated by CK2 in vivo as well as in vitro. These results suggest an important role of CK2 on promotion of cell growth through eIF5.
Homma
Miwako Kato
MK
Department of Biomolecular Sciences, Fukushima Medical University School of Medicine, 1-Hikari-gaoka, Fukushima, Japan. mkhomma@fmu.ac.jp
Homma
Yoshimi
Y
D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism; D020816:Amino Acid Motifs; D047390:Casein Kinase II / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms; D004789:Enzyme Activation; D006801:Humans; D009154:Mutation; D010448:Peptide Initiation Factors / Q000378:metabolism; D010766:Phosphorylation; D016601:RNA-Binding Proteins / Q000378:metabolism; D000097574:Eukaryotic Translation Initiation Factor 5A
D025601:Adenomatous Polyposis Coli Protein; D047390:Casein Kinase II; D010448:Peptide Initiation Factors; D016601:RNA-Binding Proteins; D000097574:Eukaryotic Translation Initiation Factor 5A