Degradation of human Lipin-1 by BTRC E3 ubiquitin ligase

Kenji Ishimoto; Ayaka Hayase; Fumiko Kumagai; Megumi Kawai; Hiroko Okuno; Nobumasa Hino; Yoshiaki Okada; Takeshi Kawamura; Toshiya Tanaka; Takao Hamakubo; Juro Sakai; Tatsuhiko Kodama; Keisuke Tachibana; Takefumi Doi

doi:10.1016/j.bbrc.2017.04.159

Degradation of human Lipin-1 by BTRC E3 ubiquitin ligase

Biochem Biophys Res Commun. 2017 Jun 17;488(1):159-164. doi: 10.1016/j.bbrc.2017.04.159. Epub 2017 May 5.

Authors

Affiliations

¹ Laboratory of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: kenji@phs.osaka-u.ac.jp.
² Laboratory of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
³ Isotope Science Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo, Tokyo 113-0032, Japan.
⁴ Laboratory for System Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153-8904, Japan.
⁵ Department of Quantitative Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153-8904, Japan.
⁶ Division of Metabolic Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153-8904, Japan.
⁷ Laboratory of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: doi@phs.osaka-u.ac.jp.

PMID: 28483528
DOI: 10.1016/j.bbrc.2017.04.159

Abstract

Lipin-1 has dual functions in the regulation of lipid and energy metabolism according to its subcellular localization, which is tightly controlled. However, it is unclear how Lipin-1 degradation is regulated. Here, we demonstrate that Lipin-1 is degraded through its DSGXXS motif. We show that Lipin-1 interacts with either of two E3 ubiquitin ligases, BTRC or FBXW11, and that this interaction is DSGXXS-dependent and mediates the attachment of polyubiquitin chains. Further, we demonstrate that degradation of Lipin-1 is regulated by BTRC in the cytoplasm and on membranes. These novel insights into the regulation of human Lipin-1 stability will be useful in planning further studies to elucidate its metabolic processes.

Keywords: BTRC; Degradation; Lipid metabolism; Lipin-1; Polyubiquitination; Protein localization.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Hep G2 Cells
Humans
Phosphatidate Phosphatase / metabolism*
Proteolysis*
Ubiquitin-Protein Ligases / metabolism*
Ubiquitination
beta-Transducin Repeat-Containing Proteins / metabolism*

Substances

BTRC protein, human
beta-Transducin Repeat-Containing Proteins
Ubiquitin-Protein Ligases
LPIN1 protein, human
Phosphatidate Phosphatase