Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
권호 표지
DOI QR코드

DOI QR Code

Effects of Proto-oncogene Protein DEK on PCAF Localization

  • Lee, In-Seon (Department of Life Science, College of Natural Sciences, Chung-Ang University) ;
  • Lee, Seok-Cheol (Department of Life Science, College of Natural Sciences, Chung-Ang University) ;
  • Lee, Jae-Hwi (Depatrment of Pharmaceuticals, College of Pharmacy, Chung-Ang University) ;
  • Seo, Sang-Beom (Department of Life Science, College of Natural Sciences, Chung-Ang University)
  • Published : 2007.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

The proto-oncogene protein DEK is a nuclear binding phosphoprotein that has been associated with various human diseases including leukemia. Histone acetylation is an important post-translational modification which plays important role in transcriptional regulation. Auto-acetylation of histone acetyltransferase PCAF results in increment of its HAT activity and facilitation of its nuclear localization. In this study, we report that DEK inhibits PCAF auto-acetylation through direct interaction. The C-terminal acidic domains of DEK are responsible for the interaction with PCAF. Using confocal microscopy, we have shown that nuclear localization of PCAF is severely inhibited by DEK. Taken together, our results suggest that DEK may be involved in various cellular signal transduction pathways accommodated by PCAF through the regulation of PCAF auto-acetylation.

Keywords

References

  1. Fornerod, M., Boer, J., van Baal, S., Jaegle, M., von Lindern, M., Murti, K.G., Davis, D., Bonten, J., Buijs, A., and Grosveld, G. (1995). Relocation of the carboxyterminal part of CAN from the nuclear envelope to the nucleus as a result of leukemia-specific chromosome rearrangements. Oncogene 10: 1739-1748
  2. Fornerod, M., Boer, J., van Baal, S., Morreau, H., and Grosveld, G. (1996). Interaction of cellular proteins with the leukemia specific fusion proteins DEK-CAN and SET-CAN and their normal counterpart, the nucleoporin CAN. Oncogene 13: 1801-1808
  3. Ko, S.I., Lee, I.S., Kim, J.Y., Kim, S.M., Kim, D.W., Lee, K.S., Woo, K.M., Baek, J.H., Choo, J.K., Seo, S.B. (2006). Regulation of histone acetyltransferase activity of p300 and PCAF by proto-oncogene protein DEK, FEBS Letters 580, 3217-3222 https://doi.org/10.1016/j.febslet.2006.04.081
  4. Krude, T. (1995). Chromatin. Nucleosome assembly during DNA replication. Curr. Biol. 5: 1232-1234 https://doi.org/10.1016/S0960-9822(95)00245-4
  5. Santos-Rosa, H., Valls, E., Kouzarides, T., and Martínez-Balbas, M. (2003). Mechanisms of P/CAF auto-acetylation. Nucleic Acids Res. 31: 4285-4292 https://doi.org/10.1093/nar/gkg655
  6. Song, C.Z., Keller, K., Murata, K., Asano, H., and Stamatoyannopoulos, G. (2002). Functional interaction between coactivators CBP/p300, PCAF and transcription factor FKLF2. J. Biol. Chem. 277: 7029-7036 https://doi.org/10.1074/jbc.M108826200
  7. Strahl, B. D., and Allis, C. D. (2000). The language of covalent histone modifications. Nature 403: 41-45 https://doi.org/10.1038/47412
  8. Struhl, K. (1998). Histone acetylation and transcriptional regulatory mechanisms. Genes Dev. 12: 599-606 https://doi.org/10.1101/gad.12.5.599
  9. Turner, B.M. (2002). Cellular memory and the histone code. Cell 111: 285-291 https://doi.org/10.1016/S0092-8674(02)01080-2
  10. von Lindern, M., Fornerod, M., van Baal, S., Jaegle, M., de Wit, T., Buijs, A., and Grosveld, G. (1992). The translocation (6;9), associated with a specific subtype of acute myeloid leukemia, results in the fusion of two genes, dek and can, and the expression of a chimeric, leukemia-specific dek-can mRNA. Mol. Cell. Biol. 12: 1687-1697 https://doi.org/10.1128/MCB.12.4.1687
  11. Yang XJ, Ogryzko VV, Nishikawa J, Howard BH, Nakatani Y. (1996) A p300/CBP-associated factor that competes with the adenoviral oncoprotein E1A. Nature. 382(6589): 319-24 https://doi.org/10.1038/382319a0