Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
권호 표지

Effects of Ser2 and Tyr6 Mutants of BAF53 on Cell Growth and p53-dependent Transcription

  • Lee, Jung Hwa (Department of Bioscience and Biotechnology, Hankuk University of Foreign Studies) ;
  • Lee, Ji Yeon (Department of Bioscience and Biotechnology, Hankuk University of Foreign Studies) ;
  • Chang, Seok Hoon (Department of Molecular Biology, Dankook University) ;
  • Kang, Mi Jin (Department of Bioscience and Biotechnology, Hankuk University of Foreign Studies) ;
  • Kwon, Hyockman (Department of Bioscience and Biotechnology, Hankuk University of Foreign Studies)
  • Received : 2004.09.15
  • Accepted : 2004.12.06
  • Published : 2005.04.30
⟨ Previous Next ⟩

Abstract

BAF53 is an actin-related protein that shuttles between nucleus and cytoplasm. In the nucleus, it constitutes an integral component of many chromatin-modifying complexes such as the SWI/SNF, TIP60, TRRAP, and TIP48/49 complexes. BAF53 is essential for growth, but its function remains elusive. BAF53 homologues from yeast to humans have a conserved N-terminal motif, MS_(G/A)(G/A)__(V/L)YGG, which is unique to these proteins. Previously we showed that over-expression of an N-terminal deletion mutant of BAF53 ($BAF53_-{\Delta}N$) reduced the viability of HEK293 and HeLa cells. When we replaced the serine 2 and tyrosine 6 of this N-terminal motif with alanine, over-expression of the alanine-replaced BAF53 strongly impaired the growth of HEK293 cells whereas replacement with aspartate/glutamate had no effect. The alanine-replaced BAF53 mutants also stimulated p53-dependent transcription, in which the SWI/SNF and TRRAP complexes are involved. Our results demonstrate that serine 2 and tyrosine 6 play important roles in BAF53 activity.

Keywords

Acknowledgement

Supported by : Korea Research Foundation

References

  1. Barlev, N. A., Liu, L., Chehab, N. H., Mansfield, K., Harris, K. G., et al. (2001) Acetylation of p53 activates transcription through recruitment of coactivators/histone acetyltransferases. Mol. Cell 8, 1243-1254 https://doi.org/10.1016/S1097-2765(01)00414-2
  2. Choi, E. Y., Park, J. A., Sung, Y. H., and Kwon, H. (2001) Generation of the dominant-negative mutant of hArpNbeta: a component of human SWI/SNF chromatin remodeling complex. Exp. Cell Res. 271, 180-188 https://doi.org/10.1006/excr.2001.5355
  3. El-Deiry, W. S., Tokino, T., Velculescu, V. E., Levy, D. B., Parsons, R., et al. (1993) WAF1, a potential mediator of p53 tumor suppression. Cell 75, 817-825 https://doi.org/10.1016/0092-8674(93)90500-P
  4. Frankel, S. and Mooseker, M. S. (1996) The actin-related proteins. Curr. Opin. Cell Biol. 8, 30-37 https://doi.org/10.1016/S0955-0674(96)80045-7
  5. Fuchs, M., Gerber, J., Drapkin, R., Sif, S., Ikura, T., et al. (2001) The p400 complex is an essential E1A transformation target. Cell 106, 297-307 https://doi.org/10.1016/S0092-8674(01)00450-0
  6. Galarneau, L., Nourani, A., Boudreault, A. A., Zhang, Y., Heliot, L., et al. (2000) Multiple links between the NuA4 histone acetyltransferase complex and epigenetic control of transcription. Mol. Cell 5, 927-937 https://doi.org/10.1016/S1097-2765(00)80258-0
  7. Ikura, T., Ogryzko, V. V., Grigoriev, M., Groisman, R., Wang, J., et al. (2000) Involvement of the TIP60 histone acetylase complex in DNA repair and apoptosis. Cell 102, 463-473 https://doi.org/10.1016/S0092-8674(00)00051-9
  8. Jiang, Y. W. and Stillman, D. J. (1996) Epigenetic effects on yeast transcription caused by mutations in an actin-related protein present in the nucleus. Genes Dev. 10, 604-619 https://doi.org/10.1101/gad.10.5.604
  9. Lee, D., Kim, J. W., Seo, T., Hwang, S. G., Choi. E. J., et al. (2002) SWI/SNF complex interacts with tumor suppressor p53 and is necessary for the activation of p53-mediated transcription. J. Biol. Chem. 277, 22330-22337 https://doi.org/10.1074/jbc.M111987200
  10. Lee, J. H., Chang, S. H., Shim, J. H., Lee, J. Y., Yoshida, M., et al. (2003) Cytoplasmic localization and nucleo-cytoplasmic shuttling of BAF53, a component of chromatin-modifying complexes. Mol. Cells 16, 78-83
  11. Metivier, R., Penot, G., Hubner, M. R., Reid, G., Brand, H., et al. (2003) Estrogen receptor-alpha directs ordered, cyclical, and combinatorial recruitment of cofactors on a natural target promoter. Cell 115, 751-763 https://doi.org/10.1016/S0092-8674(03)00934-6
  12. Shen, X., Mizuguchi, G., Hamiche, A., and Wu, C. (2000) A chromatin remodelling complex involved in transcription and DNA processing. Nature 406, 541-544 https://doi.org/10.1038/35020123
  13. Shen, X., Ranallo, R., Choi, E., and Wu, C. (2003) Involvement of actin-related proteins in ATP-dependent chromatin remodeling. Mol. Cell 12, 147-155 https://doi.org/10.1016/S1097-2765(03)00264-8
  14. Shimono, Y., Murakami, H., Kawai, K., Wade, P. A., Shimokata, K., et al. (2003) Mi-2 beta associates with BRG1 and RET finger protein at the distinct regions with transcriptional activating and repressing abilities. J. Biol. Chem. 278, 51638- 51645 https://doi.org/10.1074/jbc.M309198200
  15. Strobeck, M. W., Knudsen, K. E., Fribourg, A. F., DeCristofaro, M. F., Weissman, B. E., et al. (2000) BRG-1 is required for RB-mediated cell cycle arrest. Proc. Natl. Acad. Sci. USA 97, 7748-7753
  16. Sung, Y. H., Choi, E. Y., and Kwon, H. (2001) Identification of a nuclear protein ArpN as a component of human SWI/SNF complex and its selective association with a subset of active genes. Mol. Cells 11, 75-81
  17. Szerlong, H., Saha, A., and Cairns, B. R. (2003) The nuclear actin-related proteins Arp7 and Arp9: a dimeric module that cooperates with architectural proteins for chromatin remodeling. EMBO J. 22, 3175-3187 https://doi.org/10.1093/emboj/cdg296
  18. Wood, M. A., McMahon, S. B., and Cole, M. D. (2000) An ATPase/ helicase complex is an essential cofactor for oncogenic transformation by c-Myc. Mol. Cell 5, 321-330 https://doi.org/10.1016/S1097-2765(00)80427-X
  19. Zhang, H. S., Gavin, M., Dahiya, A., Postigo, A. A., Ma, D., et al. (2000) Exit from G1 and S phase of the cell cycle is regulated by repressor complexes containing HDAC-Rb-hSWI/ SNF and Rb-hSWI/SNF. Cell 101, 79-89 https://doi.org/10.1016/S0092-8674(00)80625-X
  20. Zhao, K., Wang, W., Rando, O. J., Xue, Y., Swiderek, K., et al. (1998) Rapid and phosphoinositol-dependent binding of the SWI/SNF-like BAF complex to chromatin after T lymphocyte receptor signaling. Cell 95, 625-636 https://doi.org/10.1016/S0092-8674(00)81633-5