Ishimoto Kenji, Hayase Ayaka, Kumagai Fumiko, Kawai Megumi, Okuno Hiroko, Hino Nobumasa, Okada Yoshiaki, Kawamura Takeshi, Tanaka Toshiya, Hamakubo Takao, Sakai Juro, Kodama Tatsuhiko, Tachibana Keisuke, Doi Takefumi
Laboratory of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
Laboratory of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
Biochem Biophys Res Commun. 2017 Jun 17;488(1):159-164. doi: 10.1016/j.bbrc.2017.04.159. Epub 2017 May 5.
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.
根据其亚细胞定位，Lipin-1在脂质和能量代谢的调节中具有双重功能，这种定位受到严格控制。然而，目前尚不清楚Lipin-1的降解是如何被调节的。在此，我们证明Lipin-1通过其DSGXXS基序被降解。我们表明，Lipin-1与两种E3泛素连接酶BTRC或FBXW11中的任何一种相互作用，并且这种相互作用依赖于DSGXXS，并介导多聚泛素链的附着。此外，我们证明Lipin-1的降解在细胞质和膜上受BTRC调节。这些关于人类Lipin-1稳定性调节的新见解将有助于规划进一步的研究以阐明其代谢过程。
