The E3 ubiquitin ligase TRIM23 regulates adipocyte differentiation via stabilization of the adipogenic activator PPARγ
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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2015-04-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/05615 |
| _version_ | 1828375562851188736 |
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| author | Masashi Watanabe Hidehisa Takahashi Yasushi Saeki Takashi Ozaki Shihori Itoh Masanobu Suzuki Wataru Mizushima Keiji Tanaka Shigetsugu Hatakeyama |
| author_facet | Masashi Watanabe Hidehisa Takahashi Yasushi Saeki Takashi Ozaki Shihori Itoh Masanobu Suzuki Wataru Mizushima Keiji Tanaka Shigetsugu Hatakeyama |
| author_sort | Masashi Watanabe |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T07:49:09Z |
| format | Article |
| id | doaj.art-b960f8fba362499787ac66381aef7c3f |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:49:09Z |
| publishDate | 2015-04-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-b960f8fba362499787ac66381aef7c3f2022-12-22T02:05:15ZengeLife Sciences Publications LtdeLife2050-084X2015-04-01410.7554/eLife.05615The E3 ubiquitin ligase TRIM23 regulates adipocyte differentiation via stabilization of the adipogenic activator PPARγMasashi Watanabe0Hidehisa Takahashi1Yasushi Saeki2Takashi Ozaki3Shihori Itoh4Masanobu Suzuki5Wataru Mizushima6Keiji Tanaka7Shigetsugu Hatakeyama8Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, JapanDepartment of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, JapanLaboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, Tokyo, JapanDepartment of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, JapanDepartment of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, JapanDepartment of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, JapanDepartment of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, JapanLaboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, Tokyo, JapanDepartment of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, JapanAdipocyte 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.https://elifesciences.org/articles/05615TRIM23ubiquitinPPARγadipocytetranscription |
| spellingShingle | Masashi Watanabe Hidehisa Takahashi Yasushi Saeki Takashi Ozaki Shihori Itoh Masanobu Suzuki Wataru Mizushima Keiji Tanaka Shigetsugu Hatakeyama The E3 ubiquitin ligase TRIM23 regulates adipocyte differentiation via stabilization of the adipogenic activator PPARγ eLife TRIM23 ubiquitin PPARγ adipocyte transcription |
| title | The E3 ubiquitin ligase TRIM23 regulates adipocyte differentiation via stabilization of the adipogenic activator PPARγ |
| title_full | The E3 ubiquitin ligase TRIM23 regulates adipocyte differentiation via stabilization of the adipogenic activator PPARγ |
| title_fullStr | The E3 ubiquitin ligase TRIM23 regulates adipocyte differentiation via stabilization of the adipogenic activator PPARγ |
| title_full_unstemmed | The E3 ubiquitin ligase TRIM23 regulates adipocyte differentiation via stabilization of the adipogenic activator PPARγ |
| title_short | The E3 ubiquitin ligase TRIM23 regulates adipocyte differentiation via stabilization of the adipogenic activator PPARγ |
| title_sort | e3 ubiquitin ligase trim23 regulates adipocyte differentiation via stabilization of the adipogenic activator pparγ |
| topic | TRIM23 ubiquitin PPARγ adipocyte transcription |
| url | https://elifesciences.org/articles/05615 |
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