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

Degradation of human Lipin-1 by BTRC E3 ubiquitin ligase.

Author information

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.

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

PMID:
28483528
DOI:
10.1016/j.bbrc.2017.04.159
[Indexed for MEDLINE]

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