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C/EBP family transcription factors are degraded by the proteasome but stabilized by forming dimer

Oncogene volume 22, pages 1273–1280 (2003)Cite this article

Abstract

CCAAT/enhancer-binding protein (C/EBP) family transcription factors are critical for transcription of several genes involved in tissue development and cellular function, proliferation, and differentiation. Here we show that inhibitory/regulatory C/EBP family proteins, Ig/EBP (C/EBPγ) and CHOP (C/EBPζ), but not positively functioning NF-IL6 (C/EBPβ), are constitutively multiubiquitinated and subsequently degraded by the proteasome. In addition, ubiquitination and degradation of these proteins are suppressed by forming dimer through their leucine zipper domains. Deletion of leucine zipper domain in NF-IL6 caused the loss of its homodimerization activity and the degradation of protein by the ubiquitin–proteasome system. In addition, Ig/EBP with its leucine zipper domain substituted for that of NF-IL6 formed homodimer and was stabilized. These observations suggest that mammalian cells equip a novel regulatory system abrogating the excess C/EBP family transcription factors bereft of dimerizing partner.

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Acknowledgements

We thank Dr M Li-Weber, Dr S Akira, and Dr D Bohmann for providing expression plasmids. This work was supported in part by Grants-in-Aid for Scientific Research (B) from Japan Society for the Promotion of Science, and Grants-in-Aid for Scientific Research on Priority Areas (C) from The Ministry of Education, Science, Sports and Culture.

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  1. Takayuki Hattori

    Present address: Department of Biochemistry 1, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan

  2. Takayuki Hattori

    Present address: CREST, Japan Science and Technology Corporation, 4-1-8 Honcho, Kawaguchi, Saitama, 332-0012, Japan

Authors and Affiliations

  1. Department of Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Nagoya City University, Mizuho, 467-8603, Nagoya, Japan

    Takayuki Hattori, Nobumichi Ohoka, Yasumichi Inoue, Hidetoshi Hayashi & Kikuo Onozaki

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  1. Takayuki Hattori
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  2. Nobumichi Ohoka
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Correspondence to Kikuo Onozaki.

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Hattori, T., Ohoka, N., Inoue, Y. et al. C/EBP family transcription factors are degraded by the proteasome but stabilized by forming dimer. Oncogene 22, 1273–1280 (2003). https://doi.org/10.1038/sj.onc.1206204

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