PML-nuclear bodies are involved in cellular serum response

Authors

  • Kazuhito Matsuzaki,

    1. Department of Regeneration Medicine, Institute of Molecular Embryology and Genetics, Kumamoto University
    2. Department of Tumor Genetics and Biology, Kumamoto University School of Medicine, 2-2-1 Honjo, Kumamoto 860-0811, Japan
    3. Department of Neurosurgery, School of Medicine, University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan
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  • Takeshi Minami,

    1. Department of Regeneration Medicine, Institute of Molecular Embryology and Genetics, Kumamoto University
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  • Masahide Tojo,

    1. Department of Regeneration Medicine, Institute of Molecular Embryology and Genetics, Kumamoto University
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  • Yoshiomi Honda,

    1. Department of Tumor Genetics and Biology, Kumamoto University School of Medicine, 2-2-1 Honjo, Kumamoto 860-0811, Japan
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  • Noriko Saitoh,

    1. Department of Regeneration Medicine, Institute of Molecular Embryology and Genetics, Kumamoto University
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  • Shinji Nagahiro,

    1. Department of Neurosurgery, School of Medicine, University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan
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  • Hideyuki Saya,

    1. Department of Tumor Genetics and Biology, Kumamoto University School of Medicine, 2-2-1 Honjo, Kumamoto 860-0811, Japan
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  • Mitsuyoshi Nakao

    Corresponding author
    1. Department of Regeneration Medicine, Institute of Molecular Embryology and Genetics, Kumamoto University
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  • Communicated by: Kozo Kaibuchi

*E-mail: mnakao@gpo.kumamoto-u.ac.jp

Abstract

Background: Serum stimulation leads to the activation of various signal transduction pathways in cells, and the resultant signals are integrated into the serum response factor (SRF)-dependent transcription of immediate-early genes such as c-fos.

Results: To further characterize this response, we investigated the mechanism which controls serum response transcription in cultured human cells. Frequency of PML (promyelocytic leukaemia)-nuclear bodies (NBs) formation increases shortly after serum stimulation, probably facilitating the interaction of SRF and CBP acetyltransferase at the NBs. PML modulates SRF-mediated c-fos promoter activities upon addition of serum to cells or expression of constitutively active Rho family GTPases. We mapped the region in the SRF that interacts with PML to the C-terminal transactivation domain. An SRF mutant deleted of the transactivation domain neither co-localizes with CBP in NBs nor fulfills its transcriptional role. Under conditions of serum stimulation, the formation of NBs coincides with the immediate-early expression of the endogenous c-fos gene in fibroblasts and in all-trans retinoic acid-treated acute promyelocytic leukaemia NB4 cells.

Conclusion: These data provide an insight into the involvement of NBs in modulating the transcription of serum-induced immediate-early genes.

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