論文 - 詳細
| RRC ID | 86822 |
|---|---|
| 著者 | Uota A, Okuno Y, Fukuhara A, Sasaki S, Kobayashi S, Shimomura I. |
| タイトル | ARMC5 selectively degrades SCAP-free SREBF1 and is essential for fatty acid desaturation in adipocytes. |
| ジャーナル | J Biol Chem |
| Abstract |
SREBF1 plays the central role in lipid metabolism. It has been known that full-length SREBF1 that did not associate with SCAP (SCAP-free SREBF1) is actively degraded, but its molecular mechanism and its biological meaning remain unclear. ARMC5-CUL3 complex was recently identified as E3 ubiquitin ligase of full-length SREBF. Although ARMC5 was involved in SREBF pathway in adrenocortical cells, the role of ARMC5 in adipocytes has not been investigated. In this study, adipocyte-specific Armc5 KO mice were generated. In the white adipose tissue of these mice, all the stearoyl-CoA desaturase (Scd) were drastically downregulated. Consistently, unsaturated fatty acids were decreased and saturated fatty acids were increased. The protein amount of full-length SREBF1 was increased, but ATAC-Seq peaks at the SREBF1-binding sites were markedly diminished around the Scd1 locus in the WAT of Armc5 KO mice. Armc5-deficient 3T3-L1 adipocytes also exhibited downregulation of Scd. Mechanistically, disruption of Armc5 restored decreased full-length SREBF1 in CHO cells deficient for Scap. Overexpression of Scap inhibited ARMC5-mediated degradation of full-length SREBF1, and overexpression of Armc5 increased nuclear SREBF1/full-length SREBF1 ratio and SREBF1 transcriptional activity in the presence of exogenous SCAP. These results demonstrated that ARMC5 selectively removes SCAP-free SREBF1 and stimulates SCAP-mediated SREBF1 processing, hence is essential for fatty acid desaturation in vivo. |
| 巻・号 | 300(12) |
| ページ | 107953 |
| 公開日 | 2024-12-1 |
| DOI | 10.1016/j.jbc.2024.107953 |
| PII | S0021-9258(24)02455-4 |
| PMID | 39491648 |
| PMC | PMC11635738 |
| MeSH | 3T3-L1 Cells* Adipocytes* / metabolism Animals Fatty Acids* / metabolism Humans Intracellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / metabolism Membrane Proteins / genetics Membrane Proteins / metabolism Mice Mice, Knockout* Proteolysis Stearoyl-CoA Desaturase* / genetics Stearoyl-CoA Desaturase* / metabolism Sterol Regulatory Element Binding Protein 1* / genetics Sterol Regulatory Element Binding Protein 1* / metabolism |
| IF | 4.238 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 6 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC01834 |