The SCFβ-TRCP E3 ubiquitin ligase complex targets Lipin1 for ubiquitination and degradation to promote hepatic lipogenesis

Kouhei Shimizu; Hidefumi Fukushima; Kohei Ogura; Evan C. Lien; Naoe Taira Nihira; Jinfang Zhang; Brian J. North; Ailan Guo; Katsuyuki Nagashima; Tadashi Nakagawa; Seira Hoshikawa; Asami Watahiki; Koji Okabe; Aya Yamada; Alex Toker; John M. Asara; Satoshi Fukumoto; Keiichi I. Nakayama; Keiko Nakayama; Hiroyuki Inuzuka; Wenyi Wei

doi:10.1126/scisignal.aah4117

Research ArticleMetabolism

The SCF^β-TRCP E3 ubiquitin ligase complex targets Lipin1 for ubiquitination and degradation to promote hepatic lipogenesis

View ORCID ProfileKouhei Shimizu¹,²,*,
Hidefumi Fukushima²,*,
Kohei Ogura¹,³,
Evan C. Lien¹,
Naoe Taira Nihira¹,
Jinfang Zhang¹,
Brian J. North¹,
Ailan Guo⁴,
Katsuyuki Nagashima⁵,
Tadashi Nakagawa⁶,
Seira Hoshikawa²,⁷,
Asami Watahiki²,
Koji Okabe⁵,
Aya Yamada⁷,
Alex Toker¹,
John M. Asara⁸,
Satoshi Fukumoto²,⁷,
Keiichi I. Nakayama⁹,
Keiko Nakayama⁶,
View ORCID ProfileHiroyuki Inuzuka¹,²,†, and
View ORCID ProfileWenyi Wei¹,†

¹Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
²Center for Advanced Stem Cell and Regenerative Research, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan.
³Department of Infectious Diseases, National Center for Global Health and Medicine, Tokyo 162-8655, Japan.
⁴Cell Signaling Technology Inc., Danvers, MA 01923, USA.
⁵Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Fukuoka 814-0193, Japan.
⁶Division of Cell Proliferation, United Centers for Advanced Research and Translational Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
⁷Division of Pediatric Dentistry, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan.
⁸Division of Signal Transduction, Beth Israel Deaconess Medical Center and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
⁹Division of Cell Regulation Systems, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.

↵†Corresponding author. Email: hinuzuka{at}bidmc.harvard.edu (H.I.); wwei2{at}bidmc.harvard.edu (W.W.)

↵* These authors contributed equally to this work.

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Science Signaling 03 Jan 2017:
Vol. 10, Issue 460, eaah4117
DOI: 10.1126/scisignal.aah4117

Kouhei Shimizu

1Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

2Center for Advanced Stem Cell and Regenerative Research, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan.

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ORCID record for Kouhei Shimizu

Hidefumi Fukushima

2Center for Advanced Stem Cell and Regenerative Research, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan.

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Kohei Ogura

1Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

3Department of Infectious Diseases, National Center for Global Health and Medicine, Tokyo 162-8655, Japan.

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Evan C. Lien

1Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

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Naoe Taira Nihira

1Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

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Jinfang Zhang

1Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

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Brian J. North

1Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

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Ailan Guo

4Cell Signaling Technology Inc., Danvers, MA 01923, USA.

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Katsuyuki Nagashima

5Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Fukuoka 814-0193, Japan.

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Tadashi Nakagawa

6Division of Cell Proliferation, United Centers for Advanced Research and Translational Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.

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Seira Hoshikawa

2Center for Advanced Stem Cell and Regenerative Research, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan.

7Division of Pediatric Dentistry, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan.

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Asami Watahiki

2Center for Advanced Stem Cell and Regenerative Research, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan.

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Koji Okabe

5Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Fukuoka 814-0193, Japan.

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Aya Yamada

7Division of Pediatric Dentistry, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan.

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Alex Toker

1Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

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John M. Asara

8Division of Signal Transduction, Beth Israel Deaconess Medical Center and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.

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Satoshi Fukumoto

2Center for Advanced Stem Cell and Regenerative Research, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan.

7Division of Pediatric Dentistry, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan.

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Keiichi I. Nakayama

9Division of Cell Regulation Systems, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.

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Keiko Nakayama

6Division of Cell Proliferation, United Centers for Advanced Research and Translational Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.

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Hiroyuki Inuzuka

1Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

2Center for Advanced Stem Cell and Regenerative Research, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan.

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For correspondence: hinuzuka@bidmc.harvard.edu wwei2@bidmc.harvard.edu

Wenyi Wei

1Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

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For correspondence: hinuzuka@bidmc.harvard.edu wwei2@bidmc.harvard.edu

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The SCF^β-TRCP E3 ubiquitin ligase complex targets Lipin1 for ubiquitination and degradation to promote hepatic lipogenesis

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