BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

The Ring-H2 Finger Motif of CKBBP1/SAG Is Necessary for Interaction with Protein Kinase CKII and Optimal Cell Proliferation

  • Kim, Yun-Sook (Department of Biochemistry, College of Natural Sciences, Kyungpook National University) ;
  • Ha, Kwon-Soo (Department of Molecular & Cellular Biochemistry, Kangwon National University, School of Medicine) ;
  • Kim, Young-Ho (Department of Microbiology, College of National Sciences, Kyungpook National University) ;
  • Bae, Young-Seuk (Department of Biochemistry, College of Natural Sciences, Kyungpook National University)
  • Published : 2002.11.30
Download PDF
⟨ Previous Next ⟩

Abstract

Protein kinase CKII (CKII) is required for progression through the cell division cycle. We recently reported that the $\beta$ subunit of protein kinase CKII ($CKII{\beta}$) associates with CKBBP1 that contains the Ring-H2 finger motif in the yeast two-hybrid system. We demonstrate here that the Ring-H2 finger-disrupted mutant of CKBBP1 does not interact with purified $CKII{\beta}$ in vitro, which shows that the Ring-H2 finger motif is critical for direct interaction with $CKII{\beta}$. The CKII holoenzyme is efficiently co-precipitated with the wild-type CKBBP1, but not with the Ring-H2 finger-disrupted CKBBP1, from whole cell extracts when epitope-tagged CKBBP1 is transiently expressed in HeLa cells. Disruption of the Ring-H2 finger motif does not affect the cellular localization of CKBBP1 in HeLa cells. The increased expression of either the wild-type CKBBP1 or Ring-H2 finger-disrupted CKBBP1 does not modulate the protein or the activity levels of CKII in HeLa cells. However, the stable expression of Ring-H2 finger-disrupted CKBBP1 in HeLa cells suppresses cell proliferation and causes the accumulation of the G1/G0 peak of the cell cycle. The Ring-H2 finger motif is required for maximal CKBBP1 phosphorylation by CKII, suggesting that the stable binding of CKBBP1 to CKII is necessary for its efficient phosphorylation. Taken together, these results suggest that the complex formation of $CKII{\beta}$ with CKBBP1 and/or CKII-mediated CKBBP1 phosphorylation is important for the G1/S phase transition of the cell cycle.

Keywords

References

  1. AIlende, J. E. and Allende, C. C. (1995) Protein kinase CK2: An enzyme with multiple substrates and a puzzling regulation. FASEB J. 9, 313-323.
  2. Chen, A., Wu, K., Fuchs, S. Y., Tan, P., Gomez, C. and Pan, Z. Q. (2000) The conserved RING-H2 finger of ROC1 is required for ubiquitin ligation. J. Biol. Chem. 275, 15432-15439. https://doi.org/10.1074/jbc.M907300199
  3. Duan, H., Wang, Y., Aviram, M., Swaroop, M., Loo, J. A., Bian, J., Tian, Y., Mueller, T., Bisgaier, C. L. and Sun, Y. (1999) SAG, a novel zinc RING finger protein that protects cells from apoptosis induced by redox agents. Mol. Cell. Biol. 19, 3145- 3155. https://doi.org/10.1128/MCB.19.4.3145
  4. Hanna, D. E., Rethinaswamy, A. and Glover, C. V. (1995) Casein kinase II is required for cell progression during Gland G2/M in Saccharomyces cerevisiae. J. BioI. Chem. 270, 25905-25914. https://doi.org/10.1074/jbc.270.43.25905
  5. Ho, S. N., Hunt, H. D., Horton, R. M., Pullen, J. K. and Pease, L. R. (1989) Site-directed mutagenesis by overlap extension using the polymerase chain reaction. Gene 77, 51-59. https://doi.org/10.1016/0378-1119(89)90358-2
  6. Issinger, O. G. (1993) Casein kinases: pleiotropic mediators of cellular regulation. Pharmacol. & Ther.59, 1-30. https://doi.org/10.1016/0163-7258(93)90039-G
  7. Jakobi, R. and Traugh, J. A. (1992) Characterization of the phosphotransferase domain of casein kinase II by site directed mutagenesis and expression in Escherichia coli. J. Biol. Chem. 267, 23894-23902.
  8. Kamura, T., Koepp, D. M., Conrad, M. N., Skowyra, D., Moreland, R. J., Iliopoulos, O., Lane, W. S., Kaelin, W. G. Jr., Elledge, S. J., Conaway, R. C., Harper, J. W. and Conaway, J. W. (1999) Rbx1, a component of the VHL tumor suppressor complex and SCF ubiquitin ligase. Science 284, 657-661. https://doi.org/10.1126/science.284.5414.657
  9. Kelliher, M. A., Seldin, D. C. and Leder, P. (1996) Tal-1 induces T cell acute lymphoblastic leukemia accelerated by casein kinase II$\alpha$. EMBO. J. 15, 5160-5166.
  10. Kim, M. -S., Lee, Y. -T., Kim, J. -M., Cha, J. -Y. and Bae, Y. -S. (1998) Characterization of protein interaction among subunits of protein kinase CKII in vivo and in vitro. Mol. Cells 8, 43- 48.
  11. Lin, W. J., Tuazon, P. T. and Traugh, J. A. (1991) Characterization of the catalytic subunit of casein kinase II expressed in Escherichia coli and regulation of activity. J. Biol. Chem. 266, 5664-5669.
  12. Munstermann, U., Fritz, G., Seitz, G., Lu, Y. P., Schneider, H. R. and Issinger, O. G. (1990) Casein kinase II is elevated in solid human tumors and proliferation non-neoplastic tissue. Eur. J. Biochem. 189, 251-257. https://doi.org/10.1111/j.1432-1033.1990.tb15484.x
  13. Ohta, T., Michel, J. J., Schottelius, A. J. and Xiong, Y. (1999) ROC1, a homolog of APC11, represents a family of cullin partners with an associated ubiquitin ligase activity. Mol. Cell. 3, 535-541. https://doi.org/10.1016/S1097-2765(00)80482-7
  14. Park, G. H. and Bae, Y. -S. (2001) Mapping of the interaction domain of DNA topoisomerase II$\alpha$ and II$\beta$ with extracellular signal-regulated kinase 2. J. Biochem. Mol. Biol. 34, 85-89.
  15. Pinna, L. A. (1990) Casein kinase 2: an eminence grise in cellular regulation? Biochim. Biophys. Acta 1054, 267-284. https://doi.org/10.1016/0167-4889(90)90098-X
  16. Ron, D. and Kazanietz, M. G. (1999) New insights into the regulation of protein kinase C and novel phorbol ester receptors. FASEB J. 13, 1658-1676.
  17. Saurin, A. J., Borden, K. L., Boddy, M. N. and Freemont, P. S. (1996) Does this have a familiar RING? Trends Biochem. Sci. 21, 208-214. https://doi.org/10.1016/0968-0004(96)10036-0
  18. Seldin, D. C. and Lecter, P. (1995) Casein kinase II$\alpha$ transgene-induced murine lymphoma: relation to theileriosis in cattle. Science 267, 894-897. https://doi.org/10.1126/science.7846532
  19. Skowyra, D., Koepp, D. M., Kamura, T., Conrad, M. N., Conaway, R. C., Conaway, J. W., Elledge, S. J. and Harper, J. W. (1999) Reconstitution of G1 cyclin ubiquitination with complexes containing $SCF^{Grrl}$ and Rbx1. Science 184, 662-665, https://doi.org/10.1126/science.284.5414.662
  20. Son, M. -Y., Park, J. -W., Kim, Y. -S., Kang, S. -W., Marshak, D. R., Park, W. and Bae, Y. -S. (1999) ProIein kinase CKlI interacts with and phosphorylates the SAG protein containing Ring-H2 finger motif. Biochem. Biophys. Res. Commun. 263, 743-748. https://doi.org/10.1006/bbrc.1999.1460
  21. Swaroop, M., Bian, J., Aviram, M., Duan, H., Bisgaier, C. L., Loo, J. A. and Sun, Y. (1999) Expression, purification, and biochemical characterization of SAG, a ring finger redox-sensitive protein. Free Radic. Biol. Med. 27, 193-202. https://doi.org/10.1016/S0891-5849(99)00078-7
  22. swaroop, M., Wang, Y., Miller, P., Duan, H., Jatkoe, T., Madore, S. J. and Sun, Y. (2000) Yeast homolog of human SAG/ROC2/ Rbx2/Hrt2 is essential for cell growth, but not for germination: chip profiling implicates its role in cell cycle regulation. Oncogene 19, 2855-2866. https://doi.org/10.1038/sj.onc.1203635
  23. Yi, J. Y., Hong, W. -S. and Son, Y. S. (2001) Biochemical characterization of adriamycin-resistance in PC-14 human lung adenocarcinoma cell line, J. Biochem. Mol. Biol. 34, 66-72.

Cited by

  1. Identification of Mutations in Protein Kinase CKIIβ Subunit That Affect Its Binding to Ribosomal Protein L41 and Homodimerization vol.36, pp.4, 2003, https://doi.org/10.5483/BMBRep.2003.36.4.344
  2. Production of Nuclease Activity in U937 Cells by Phorbol 12-Myristate 13-Acetate and Lipopolysaccharide vol.36, pp.5, 2003, https://doi.org/10.5483/BMBRep.2003.36.5.520
  3. Asparagine-473 Residue Is Important to the Efficient Function of Human Dihydrolipoamide Dehydrogenase vol.38, pp.2, 2005, https://doi.org/10.5483/BMBRep.2005.38.2.248