Maturation and activity of sterol regulatory element binding protein 1 is inhibited by acyl-CoA binding domain containing 3.
Maturation and activity of sterol regulatory element binding protein 1 is inhibited by acyl-CoA binding domain containing 3.
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固醇调节元素结合蛋白1的成熟和活性被含有3的酰基-COA结合结构域抑制。
DOI：
10.1371/journal.pone.0049906
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Kim SF
中科院分区：
文献类型：
--
作者：
Chen Y;Patel V;Bang S;Cohen N;Millar J;Kim SF
Imbalance of lipid metabolism has been linked with pathogenesis of a variety of human pathological conditions such as diabetes, obesity, cancer and neurodegeneration. Sterol regulatory element binding proteins (SREBPs) are the master transcription factors controlling the homeostasis of fatty acids and cholesterol in the body. Transcription, expression, and activity of SREBPs are regulated by various nutritional, hormonal or stressful stimuli, yet the molecular and cellular mechanisms involved in these adaptative responses remains elusive. In the present study, we found that overexpressed acyl-CoA binding domain containing 3 (ACBD3), a Golgi-associated protein, dramatically inhibited SREBP1-sensitive promoter activity of fatty acid synthase (FASN). Moreover, lipid deprivation-stimulated SREBP1 maturation was significantly attenuated by ACBD3. With cell fractionation, gene knockdown and immunoprecipitation assays, it was showed that ACBD3 blocked intracellular maturation of SREBP1 probably through directly binding with the lipid regulator rather than disrupted SREBP1-SCAP-Insig1 interaction. Further investigation revealed that acyl-CoA domain-containing N-terminal sequence of ACBD3 contributed to its inhibitory effects on the production of nuclear SREBP1. In addition, mRNA and protein levels of FASN and de novo palmitate biosynthesis were remarkably reduced in cells overexpressed with ACBD3. These findings suggest that ACBD3 plays an essential role in maintaining lipid homeostasis via regulating SREBP1's processing pathway and thus impacting cellular lipogenesis.
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影响因子：
4.8
作者：
Hannah, VC;Ou, JF;Brown, MS
通讯作者：
Brown, MS
影响因子：
15.9
作者：
Kammoun, Helene L.;Chabanon, Herve;Foufelle, Fabienne
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影响因子：
13.6
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Fan, Jinjiang;Liu, Jun;Culty, Martine;Papadopoulos, Vassilios
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Papadopoulos, Vassilios
影响因子：
4.8
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Lee, JN;Ye, J
通讯作者：
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影响因子：
4.1
作者：
Elle, Ida C.;Simonsen, Karina T.;Faergeman, Nils J.
通讯作者：
Faergeman, Nils J.