SPRING off the lock: SPRING在S1P活性和srebp调节的脂质代谢中的作用。

IF 4.6 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Current opinion in lipidology Pub Date : 2025-10-01 Epub Date: 2025-08-01 DOI:10.1097/MOL.0000000000001003
Ilaria Micallo, Ashley V Bullington, Daniel L Kober, Noam Zelcer
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引用次数: 0

摘要

综述目的:脂质代谢和去新生脂肪生成(DNL)广泛受SREBP转录因子控制。这些转录因子通过蛋白酶S1P和S2P的蛋白水解作用从膜锚定的前体蛋白成熟。在这篇综述中,我们总结了目前对SPRING的理解,SPRING是最近发现的S1P激活剂。最近的发现:最近使用动物、细胞、生化和生物物理方法对SPRING进行的研究已经确定SPRING是SREBP机制的核心组成部分。在细胞和动物肝脏中删除SPRING会特异性地降低SREBP活性,但会使其他S1P底物保持完整,这表明SPRING在S1P活性中具有SREBP特异性作用。机械生化和结构研究表明,SPRING通过竞争性取代S1P的抑制前结构域来激活S1P,并阐明了S1P的小分子抑制是如何实现的。摘要:目前的研究已经揭示了SPRING如何激活S1P,并揭示了SPRING在SREBP通路中的关键作用。需要进一步的研究来理解SPRING与通过SREBP调控DNL之间的联系。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

SPRINGing off the lock: the role of SPRING in S1P activity and SREBP-regulated lipid metabolism.

SPRINGing off the lock: the role of SPRING in S1P activity and SREBP-regulated lipid metabolism.

SPRINGing off the lock: the role of SPRING in S1P activity and SREBP-regulated lipid metabolism.

SPRINGing off the lock: the role of SPRING in S1P activity and SREBP-regulated lipid metabolism.

Purpose of review: Lipid metabolism and de-novo lipogenesis (DNL) is broadly controlled by the SREBP transcription factors. These transcription factors are matured from membrane-anchored precursor proteins by the proteolytic actions of the proteases S1P and S2P. In this review, we summarize the current understanding of SPRING, a recently identified activator of S1P.

Recent findings: Recent studies of SPRING using animal, cellular, biochemical, and biophysical methods have established SPRING as a core component of the SREBP machinery. Deletion of SPRING in cells and animal livers specifically reduces SREBP activity yet leaves other S1P substrates intact, demonstrating an SREBP-specific role for SPRING in licensing S1P activity. Mechanistic biochemical and structural studies revealed that SPRING activates S1P by competitively displacing its inhibitory pro-domain and elucidated how small molecule inhibition of S1P can be accomplished.

Summary: Current studies have shown how SPRING activates S1P and uncovered a critical role for SPRING in the SREBP pathway. Further studies are warranted to understand this emerging, connection between SPRING and the regulation of DNL through SREBP.

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来源期刊
Current opinion in lipidology
Current opinion in lipidology 医学-内分泌学与代谢
CiteScore
6.70
自引率
4.50%
发文量
64
审稿时长
6-12 weeks
期刊介绍: With its easy-to-digest reviews on important advances in world literature, Current Opinion in Lipidology offers expert evaluation on a wide range of topics from six key disciplines including nutrition and metabolism, genetics and molecular biology, and hyperlipidaemia and cardiovascular disease. Published bimonthly, each issue covers in detail the most pertinent advances in these fields from the previous year. This is supplemented by a section of Bimonthly Updates, which deliver an insight into new developments at the cutting edge of the disciplines covered in the journal.
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