1. Biochemistry and Chemical Biology
  2. Cell Biology
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The E3 ubiquitin ligase TRIM23 regulates adipocyte differentiation via stabilization of the adipogenic activator PPARγ

  1. Masashi Watanabe
  2. Hidehisa Takahashi
  3. Yasushi Saeki
  4. Takashi Ozaki
  5. Shihori Itoh
  6. Masanobu Suzuki
  7. Wataru Mizushima
  8. Keiji Tanaka
  9. Shigetsugu Hatakeyama  Is a corresponding author
  1. Hokkaido University Graduate School of Medicine, Japan
  2. Tokyo Metropolitan Institute of Medical Science, Japan
Research Article
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Cite this article as: eLife 2015;4:e05615 doi: 10.7554/eLife.05615

Abstract

Adipocyte differentiation is a strictly controlled process regulated by a series of transcriptional activators. Adipogenic signals activate early adipogenic activators and facilitate the transient formation of early enhanceosomes at target genes. These enhancer regions are subsequently inherited by late enhanceosomes. PPARγ is one of the late adipogenic activators and is known as a master regulator of adipogenesis. However, the factors that regulate PPARγ expression remain to be elucidated. Here, we show that a novel ubiquitin E3 ligase, tripartite motif protein 23 (TRIM23), stabilizes PPARγ protein and mediates atypical polyubiquitin conjugation. TRIM23 knockdown caused a marked decrease in PPARγ protein abundance during preadipocyte differentiation, resulting in a severe defect in late adipogenic differentiation, whereas it did not affect the formation of early enhanceosomes. Our results suggest that TRIM23 plays a critical role in the switching from early to late adipogenic enhanceosomes by stabilizing PPARγ protein possibly via atypical polyubiquitin conjugation.

Article and author information

Author details

  1. Masashi Watanabe

    Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Japan
    Competing interests
    The authors declare that no competing interests exist.
  2. Hidehisa Takahashi

    Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Japan
    Competing interests
    The authors declare that no competing interests exist.
  3. Yasushi Saeki

    Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
    Competing interests
    The authors declare that no competing interests exist.
  4. Takashi Ozaki

    Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Japan
    Competing interests
    The authors declare that no competing interests exist.
  5. Shihori Itoh

    Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Japan
    Competing interests
    The authors declare that no competing interests exist.
  6. Masanobu Suzuki

    Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Japan
    Competing interests
    The authors declare that no competing interests exist.
  7. Wataru Mizushima

    Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Japan
    Competing interests
    The authors declare that no competing interests exist.
  8. Keiji Tanaka

    Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
    Competing interests
    The authors declare that no competing interests exist.
  9. Shigetsugu Hatakeyama

    Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Japan
    For correspondence
    hatas@med.hokudai.ac.jp
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: Animal experimentation: All animal protocols were reviewed and approved by the Animal Welfare Committee of Hokkaido University. The work presented in this study is covered by the Animal Protocol Numbers APN-10-0077 and APN13-0040. All researchers, who performed procedures using live animal, were pre-approved by the Animal Welfare Committee of Hokkaido University, based on their completion of required animal use and care training, and acceptable previous experience in animal experiments.

Reviewing Editor

  1. Michael Czech, University of Massachusetts Medical School, United States

Publication history

  1. Received: November 13, 2014
  2. Accepted: April 21, 2015
  3. Accepted Manuscript published: April 23, 2015 (version 1)
  4. Version of Record published: May 11, 2015 (version 2)

Copyright

© 2015, Watanabe et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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