CGI-58: Versatile Regulator of Intracellular Lipid Droplet Homeostasis.
CGI-58: Versatile Regulator of Intracellular Lipid Droplet Homeostasis.
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DOI：
10.1007/978-981-15-6082-8_13
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发表时间：
2020
影响因子：
--
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Yu L;Li Y;Grisé A;Wang H
比较基因鉴定-58（CGI-58），也称为α/β-水解酶结构域5（ABHD 5），是一个含有α/β-水解酶折叠的蛋白质大家族的成员。CGI-58是脂肪甘油三酯脂肪酶（ATGL）的共激活剂，ATGL是启动细胞内脂滴脂解的关键酶。人CGI-58或ATGL基因的突变引起常染色体隐性中性脂质储存病，其特征在于几乎所有细胞类型的细胞质中富含甘油三酯（TAG）的脂滴的过度积累。然而，CGI-58具有独立于ATGL的功能。与CGI-58缺乏相关的不同表型通常包括鱼鳞病（鳞状干燥皮肤），非酒精性脂肪性肝炎和肝纤维化。通过调节与多个蛋白质家族的相互作用，CGI-58控制许多代谢和信号传导途径，如脂质和葡萄糖代谢，能量平衡，胰岛素信号传导，炎症反应和产热。最近的研究表明，CGI-58以组织特异性方式调节常见代谢疾病的发病机制。未来的研究需要从分子上定义CGI-58的ATGL独立功能，包括新鉴定的CGI-58的丝氨酸蛋白酶活性。阐明CGI-58的这些多功能可能会揭示控制脂质和能量稳态的基本细胞过程，这可能有助于开发对抗肥胖及其相关代谢后遗症的新方法。
Comparative gene identification-58 (CGI-58), also known as α/β-hydrolase domain-containing 5 (ABHD5), is a member of a large family of proteins containing an α/β-hydrolase-fold. CGI-58 is well-known as the co-activator of adipose triglyceride lipase (ATGL), which is a key enzyme initiating cytosolic lipid droplet lipolysis. Mutations in either the human CGI-58 or ATGL gene cause an autosomal recessive neutral lipid storage disease, characterized by the excessive accumulation of triglyceride (TAG)-rich lipid droplets in the cytoplasm of almost all cell types. CGI-58, however, has ATGL-independent functions. Distinct phenotypes associated with CGI-58 deficiency commonly include ichthyosis (scaly dry skin), nonalcoholic steatohepatitis, and hepatic fibrosis. Through regulated interactions with multiple protein families, CGI-58 controls many metabolic and signaling pathways, such as lipid and glucose metabolism, energy balance, insulin signaling, inflammatory responses, and thermogenesis. Recent studies have shown that CGI-58 regulates the pathogenesis of common metabolic diseases in a tissue-specific manner. Future studies are needed to molecularly define ATGL-independent functions of CGI-58, including the newly identified serine protease activity of CGI-58. Elucidation of these versatile functions of CGI-58 may uncover fundamental cellular processes governing lipid and energy homeostasis, which may help develop novel approaches that counter against obesity and its associated metabolic sequelae.
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DOI：
10.1074/jbc.m115.682203
发表时间：
2015-10-30
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Boeszoermenyi A;Nagy HM;Arthanari H;Pillip CJ;Lindermuth H;Luna RE;Wagner G;Zechner R;Zangger K;Oberer M
通讯作者：
Oberer M
影响因子：
6.5
作者：
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通讯作者：
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影响因子：
6.5
作者：
Brown, J. Mark;Chung, Soonkyu;Yu, Liqing
通讯作者：
Yu, Liqing
DOI：
10.1016/j.bbrc.2008.10.081
发表时间：
2008-12-19
影响因子：
3.1
作者：
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通讯作者：
Arca, Marcello
影响因子：
16
作者：
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通讯作者：
Kahn, CR