Cholesterol-Independent SREBP-1 Maturation Is Linked to ARF1 Inactivation
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Authors
Smulan, Lorissa J.Ding, Wei
Freinkman, Elizaveta
Gujja, Sharvari
Edwards, Yvonne J. K
Walker, Amy K
Document Type
Journal ArticlePublication Date
2016-06-28Keywords
Biochemistry
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Lipogenesis requires coordinated expression of genes for fatty acid, phospholipid, and triglyceride synthesis. Transcription factors, such as SREBP-1 (Sterol regulatory element binding protein), may be activated in response to feedback mechanisms linking gene activation to levels of metabolites in the pathways. SREBPs can be regulated in response to membrane cholesterol and we also found that low levels of phosphatidylcholine (a methylated phospholipid) led to SBP-1/SREBP-1 maturation in C. elegans or mammalian models. To identify additional regulatory components, we performed a targeted RNAi screen in C. elegans, finding that both lpin-1/Lipin 1 (which converts phosphatidic acid to diacylglycerol) and arf-1.2/ARF1 (a GTPase regulating Golgi function) were important for low-PC activation of SBP-1/SREBP-1. Mechanistically linking the major hits of our screen, we find that limiting PC synthesis or LPIN1 knockdown in mammalian cells reduces the levels of active GTP-bound ARF1. Thus, changes in distinct lipid ratios may converge on ARF1 to increase SBP-1/SREBP-1 activity.Source
Cell Rep. 2016 Jun 28;16(1):9-18. doi: 10.1016/j.celrep.2016.05.086. Epub 2016 Jun 16. Link to article on publisher's siteDOI
10.1016/j.celrep.2016.05.086Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39996PubMed ID
27320911Related Resources
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This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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http://creativecommons.org/licenses/by-nc-nd/4.0/ae974a485f413a2113503eed53cd6c53
10.1016/j.celrep.2016.05.086
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Except where otherwise noted, this item's license is described as <p>This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).</p>