The E3 ubiquitin ligase TRIM23 regulates adipocyte differentiation via stabilization of the adipogenic activator PPARgamma

• Project/Area Number: 25860201
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Hokkaido University
• Principal Investigator: WATANABE masashi 北海道大学, 医学(系)研究科(研究院), 助教 (10632424)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: ユビキチン / PPARガンマー / ユビキチンリガーゼ / 医化学

Outline of Final Research Achievements

Adipocyte differentiation is a tightly controlled process regulated by complex transcriptional activators. Multiple adipogenic signals activate early adipogenic activators and facilitate the transient formation of early enhanceosomes at target genes. These enhancer regions are subsequently inherited by the late adipogenic activators, which coordinate the formation of late enhanceosomes. PPARgamma is one of the late adipogenic activators and is considered the master regulator of adipogenesis. We showed that a novel ubiquitin E3 ligase, tripartite motif protein 23 (TRIM23), stabilizes PPARgamma protein and mediates atypical polyubiquitin conjugation. TRIM23 knockdown caused a marked decrease in PPARgamma protein abundance during preadipocyte differentiation, resulting in a severe defect in late adipogenic differentiation, whereas it did not affect the formation of early enhanceosomes. This adipogenic defect is rescued by ectopic expression of PPARgamma.

Research Products

• [Journal Article] The E3 ubiquitin ligase TRIM23 regulates adipocyte differentiation via stabilization of the adipocyte activator PPAR gamma. (2015)
  • Author(s): Watanabe, M., Takahashi, H., Saeki, Y., Ozaki, T., Itoh, S., Suzuki, M., Mizushima, W., Tanaka, K. and Hatakeyama, S.
  • Journal Title: eLIFE Volume: 4
  • DOI: 10.7554/elife.05615
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] MED26 regulates the transcription of snRNA genes through the recruitment of little elongation complex (2015)
  • Author(s): Takahashi, H., Takigawa, I., Watanabe, M., Anwar, D., Shibata, M., Tomomori-Sato, C., Sato, S., Ranjan, A., Seidel, C.W., Tsukiyama, T., Mizushima, W., Hayashi, M., Ohkawa, Y., Conaway, J.W., Conaway, R.C. and Hatakeyama, S
  • Journal Title: Nature Commun. Volume: 5 Issue: 1 Pages: 5941-5941
  • DOI: 10.1038/ncomms6941
  • NAID: 120005621881
  • Peer Reviewed / Open Access
• [Journal Article] Pathology of frontotemporal dementia with limb girdle muscular dystrophy caused by DNAJB6 mutation (2014)
  • Author(s): Yabe, I., Tanino, M., Yaguchi, H., Takiyama, A., Cai, H., Kanno, H., Takahashi, I., Hayashi, Y., Watanabe, M., Takahashi, H., Hatakeyama, S., Tanaka, S. and Sasaki, H.
  • Journal Title: Clin. Neurol. Neurosur. Volume: 127 Pages: 10-12
  • DOI: 10.1016/j.clineuro.2014.09.013
  • NAID: 120005540291
  • Peer Reviewed / Open Access
• [Journal Article] TRIM29 as a novel prostate basal cell marker for diagnosis of prostate cancer (2014)
  • Author(s): Kanno, Y., Watanabe, M., Kimura, T., Nonomura, K., Tanaka, S. and Hatakeyama, S
  • Journal Title: Acta Histochem Volume: 116 Issue: 5 Pages: 708-712
  • DOI: 10.1016/j.acthis.2013.12.009
  • NAID: 120005472205
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] TRIM23 is required for expression of peroxisome proliferator-activated receptor-γ and for subsequent adipocyte differentiation (2014)
  • Author(s): Masashi Watanabe, Hidehisa Takahashi, Shigetsugu Hatakeyama
  • Organizer: 日本分子生物学会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-11-25
• [Presentation] Tripartite motif protein 23 regulates adipocyte differentiation via stabilizing PPARγ (2014)
  • Author(s): Masashi Watanabe
  • Organizer: Symposium for young ubiquitin researchers in Japan “New Era in the Ubiquitin Research”
  • Place of Presentation: 国際高等研究所
  • Year and Date: 2014-11-11
• [Presentation] TRIMタンパク質による脂肪細胞分化制御 (2014)
  • Author(s): 渡部 昌, 高橋秀尚, 畠山鎮次
  • Organizer: 日本生化学会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2014-10-18
• [Presentation] Involvement of linear polyubiquitylation in PPARg transcriptional activity (2013)
  • Author(s): Masashi Watanabe
  • Organizer: Cold Spring Harbor Laboratory Meeting
  • Place of Presentation: Cold Spring Harbor, New York