Identification of mouse Prp19p as a lipid droplet-associated protein and its possible involvement in the biogenesis of lipid droplets
Identification of mouse Prp19p as a lipid droplet-associated protein and its possible involvement in the biogenesis of lipid droplets
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DOI：
10.1074/jbc.m608042200
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发表时间：
2007-01-26
影响因子：
4.8
通讯作者：
Lee, Tae Ryong
中科院分区：
文献类型：
--
作者：
Cho, Si Young;Shin, Eui Seok;Lee, Tae Ryong
Prp 19 p是细胞核中异聚体蛋白复合物（NineTeen复合物）的组成部分，它对NineTeen复合物的结构完整性及其随后的剪接体激活至关重要。我们确定了Prp 19 p，这是从来没有报道过的核外的任何功能，作为与脂滴相关的蛋白质的成员。在3 T3-L1细胞中用RNA干扰下调Prp 19 p表达抑制了脂滴形成，降低了围脂蛋白和S3-12的表达水平。在Prp 19 p下调的细胞中，SCD 1（硬脂酰辅酶A去饱和酶-1）、DGAT-1（酰基辅酶A二酰基甘油酰基转移酶-1）和甘油-3-磷酸酰基转移酶的表达水平也降低，并且观察到甘油三酯显著降低。不像perilipin，这是一个最广泛的研究脂滴相关蛋白，Prp 19 p是不是必不可少的cAMP和cAMP敏感的脂肪酶依赖的脂解途径，即使Prp 19 p是一个组成部分的脂滴磷脂单层，和Prp 19 p的下调抑制脂肪增生显着。这些结果表明，Prp 19 p或Prp 19-脂肪细胞中的脂滴生物合成过程中的相互作用的蛋白质可以被认为是另一类潜在的目标，攻击肥胖和肥胖相关的问题。
Prp19p is an integral component of the heteromeric protein complex (the NineTeen complex) in the nucleus, and it is essential for the structural integrity of NineTeen complex and its subsequent activation of the spliceosome. We identified Prp19p, which has never been reported in relation to any function outside of the nucleus, as a member of proteins associated with lipid droplets. Down-regulation of Prp19p expression with RNA interference in 3T3-L1 cells repressed lipid droplet formation with the reduction in the level of expression of perilipin and S3-12. The levels of expression of SCD1 (stearoyl-CoA desaturase-1), DGAT-1 (acyl-CoA diacylglycerol acyltransferase-1), and glycerol-3-phosphate acyltransferase were also reduced in Prp19p down-regulated cells, and a significant decrease in triglycerides was observed. Unlike perilipin, which is one of the most extensively studied lipid droplet-associated proteins, Prp19p is not essential for cAMP- and hormone-sensitive lipase-dependent lipolysis pathways, even though Prp19p is a component of the lipid droplet phospholipid monolayer, and down-regulation of Prp19p represses fat accretion significantly. These results suggest that Prp19p or Prp19-interacting proteins during lipid droplet biogenesis in adipocytes may be considered as another class of potential targets for attacking obesity and obesity-related problems.