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Prothymosin alpha interacts with C-terminal domain of histone H1 and dissociates p53-histone H1 complex

  • Molecular Biology of the Cell
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Abstract

A novel mode of tumor suppressor protein p53 regulation, mediated by recruitment of the linker histone H1 to the promoters of p53 target genes leading to specific repression of p53-dependent transcription, has recently been uncovered. Yet, how this repression could be relieved is not clear. Previously, a histone-binding nuclear protein prothymosin alpha (ProTa) was shown to trigger a p53 response. The histone-binding region of ProTa was found to be essential for this effect, allowing for the possibility that ProTa stimulates p53-dependent transcription by dissociating the p53-histone H1 repressive complex. In support of this model, here we show that ProTa interacts with the same C-terminal domain of histone H1 as p53 does and, therefore, ProTa and p53 could compete for binding to histone H1. Furthermore, ProTa, when competent for histone H1 binding, is able to liberate p53 from the histone H1-p53 complex in vitro. In vivo, stimulation of p53-dependent transcription by ProTa correlates with the ability of ProTa to interact with histone H1. Ectopic expression of histone H1 or its C-terminal ProTa-binding domain specifically suppresses the stimulating effect of ProTa on transcription of the p53-responsive reporter gene in cultured cells. These results are consistent with the model that ProTa may enhance p53 transcription activity by displacement of histone H1 from p53-H1 repressive complex.

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Abbreviations

ProTa:

prothymosin alpha

NLS:

nuclear localization signal

GH1:

globular domain of histone H1

CBP:

CREB-binding protein

aa’s:

amino acid residues

SDS:

sodium dodecyl sulfate

PAGE:

polyacrylamide gel electrophoresis

PMSF:

phenylmethylsulfonyl fluoride

References

  1. Chumakov P.M. 2007. The p53 protein and its universal functions in a multicellular organism. Usp. Biol. Khim. 47, 3–52.

    CAS  Google Scholar 

  2. Letsas K.P., Frangou-Lazaridis M. 2006. Surfing on prothymosin alpha proliferation and anti-apoptotic properties. Neoplasma. 53, 92–96.

    PubMed  CAS  Google Scholar 

  3. Vartapetian A.B., Uversky V.N. 2003. Prothymosin alpha: A simple yet mysterious protein. In: Protein Structures: Kaleidoscope of Structural Properties and Functions. Trivandrum, India: Research Signpost, pp. 223–237.

    Google Scholar 

  4. Jiang X., Kim H.E., Shu H., Zhao Y., Zhang H., Kofron J., Donnelly J., Burns D., Ng S.C., Rosenberg S., Wang X. 2003. Distinctive roles of PHAP proteins and prothymosin-alpha in a death regulatory pathway. Science. 299, 223–226.

    Article  PubMed  CAS  Google Scholar 

  5. Evstafieva A.G., Belov G.A., Rubtsov Y.P., Kalkum M., Joseph B., Chichkova N.V., Sukhacheva E.A., Bogdanov A.A., Pettersson R.F., Agol V.I., Vartapetian A.B. 2003. Apoptosis-related fragmentation, translocation, and properties of human prothymosin alpha. Exp. Cell Res. 284, 211–223.

    Article  PubMed  CAS  Google Scholar 

  6. Kobayashi T., Wang T., Maezawa M., Kobayashi M., Ohnishi S., Hatanaka K., Hige S., Shimizu Y., Kato M., Asaka M., Tanaka J., Imamura M., Hasegawa K., Tanaka Y., Brachmann R.K. 2006. Overexpression of the oncoprotein prothymosin alpha triggers a p53 response that involves p53 acetylation. Cancer Res. 66, 3137–3144.

    Article  PubMed  CAS  Google Scholar 

  7. Zakharova N.I., Sokolov V.V., Roudko V.V., Melnikov S.V., Vartapetian A.B., Evstafieva A.G. 2008. Effect of prothymosin α and its mutants on the activity of the p53 tumor suppressor. Mol. Biol. (Moscow). 42, 598–608.

    Article  CAS  Google Scholar 

  8. Karetsou Z., Kretsovali A., Murphy C., Tsolas O., Papamarcaki T. 2002. Prothymosin alpha interacts with the CREB-binding protein and potentiates transcription. EMBO Rep. 3, 361–366.

    Article  PubMed  CAS  Google Scholar 

  9. Subramanian C., Hasan S., Rowe M., Hottiger M., Orre R., Robertson E.S. 2002. Epstein-Barr virus nuclear antigen 3C and prothymosin alpha interact with the p300 transcriptional coactivator at the CH1 and CH3/HAT domains and cooperate in regulation of transcription and histone acetylation. J. Virol. 76, 4699–4708.

    Article  PubMed  CAS  Google Scholar 

  10. Papamarcaki T., Tsolas O. 1994. Prothymosin alpha binds to histone H1 in vitro. FEBS Lett. 345, 71–75.

    Article  PubMed  CAS  Google Scholar 

  11. Díaz-Jullien C., Pérez-Estévez A., Covelo G., Freire M. 1996. Prothymosin alpha binds histones in vitro and shows activity in nucleosome assembly assay. Biochim. Biophys. Acta. 1296, 219–227.

    Article  PubMed  Google Scholar 

  12. Karetsou Z., Sandaltzopoulos R., Frangou-Lazaridis M., Lai C.Y., Tsolas O., Becker P.B., Papamarcaki T. 1998. Prothymosin alpha modulates the interaction of histone H1 with chromatin. Nucleic Acids Res. 26, 3111–3118.

    Article  PubMed  CAS  Google Scholar 

  13. George E.M., Brown D.T. 2010. Prothymosin alpha is a component of a linker histone chaperone. FEBS Lett. 584, 2833–2836.

    Article  PubMed  CAS  Google Scholar 

  14. Kim K., Choi J., Heo K., Kim H., Levens D., Kohno K., Johnson E.M., Brock H.W., An W. 2008. Isolation and characterization of a novel H1.2 complex that acts as a repressor of p53-mediated transcription. J. Biol. Chem. 283, 9113–9126.

    Article  PubMed  CAS  Google Scholar 

  15. Nishiyama M., Oshikawa K., Tsukada Y., Nakagawa T., Iemura S., Natsume T., Fan Y., Kikuchi A., Skoultchi A.I., Nakayama K.I. 2009. CHD8 suppresses p53-mediated apoptosis through histone H1 recruitment during early embryogenesis. Nature Cell. Biol. 11, 172–182.

    Article  PubMed  CAS  Google Scholar 

  16. Tolskaya E.A., Romanova L.I., Kolesnikova M.S., Ivannikova T.A., Smirnova E.A., Raikhlin N.T., Agol V.I. 1995. Apoptosis-inducing and apoptosis-preventing functions of poliovirus. J. Virol. 69, 1181–1189.

    PubMed  CAS  Google Scholar 

  17. Evstafieva A.G., Chichkova N.V., Makarova T.N., Vartapetian A.B., Vasilenko A.V., Abramov V.M., Bogdanov A.A. 1995. Overproduction in Escherichia coli, purification, and properties of human prothymosin alpha. Eur. J. Biochem. 231, 639–643.

    Article  PubMed  CAS  Google Scholar 

  18. Evstafieva A.G., Belov G.A., Kalkum M., Chichkova N.V., Bogdanov A.A., Agol V.I., Vartapetian A.B. 2000. Prothymosin alpha fragmentation in apoptosis. FEBS Lett. 467, 150–154.

    Article  PubMed  CAS  Google Scholar 

  19. Chichkova N.V., Evstafieva A.G., Lyakhov I.G., Tsvetkov A.S., Smirnova T.A., Karapetian R.N., Karger E.M., Vartapetian A.B. 2000. Divalent metal cation binding properties of human prothymosin α. Eur. J. Biochem. 267, 4745–4752.

    Article  PubMed  CAS  Google Scholar 

  20. Sukhacheva E.A., Evstafieva A.G., Fateeva T.V., Shakulov V.R., Efimova N.A., Karapetian R.N., Rubtsov Y.P., Vartapetian A.B. 2002. Sensing prothymosin alpha origin, mutations and conformation with monoclonal antibodies. J. Immunol. Meth. 266, 185–196.

    Article  CAS  Google Scholar 

  21. McBryant S.J., Xu Lu, Hansen J.C. 2010. Multifunctionality of the linker histones: An emerging role for protein-protein interactions. Cell Res. 20, 519–528.

    Article  PubMed  CAS  Google Scholar 

  22. Catez F., Ueda T., Bustin M. 2006. Determinants of histone H1 mobility and chromatin binding in living cells. Nature Struct. Mol. Biol. 13, 305–310.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Belozersky Institute of Physicochemical Biology, Moscow State University, Moscow, Russia

    A. G. Evstafieva

  2. Department of Bioengineering and Bioinformatics, Moscow State University, Moscow, Russia

    N. I. Zakharova, V. V. Sokolov, A. A. Suvorova & A. G. Evstafieva

  3. Department of Microbiology and Immunology, National Cheng Kung University Medical College, Tainan, Taiwan

    Ai-Li Shiau

  4. Department of Biochemistry and Molecular Biology, National Cheng Kung University Medical College, Tainan, Taiwan

    Chao-Liang Wu

Authors
  1. N. I. Zakharova
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  2. V. V. Sokolov
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  3. A. A. Suvorova
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  4. Ai-Li Shiau
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  5. Chao-Liang Wu
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  6. A. G. Evstafieva
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Corresponding author

Correspondence to A. G. Evstafieva.

Additional information

Original Russian Text © N.I. Zakharova, V.V. Sokolov, A.A. Suvorova, Ai-Li Shiau, Chao-Liang Wu, A.G. Evstafieva, 2011, published in Molekulyarnaya Biologiya, 2011, Vol. 45, No. 4, pp. 679–688.

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Zakharova, N.I., Sokolov, V.V., Suvorova, A.A. et al. Prothymosin alpha interacts with C-terminal domain of histone H1 and dissociates p53-histone H1 complex. Mol Biol 45, 624–633 (2011). https://doi.org/10.1134/S0026893311040157

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  • DOI: https://doi.org/10.1134/S0026893311040157

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