The cholesterol-regulated StarD4 gene encodes a StAR-related lipid transfer protein with two closely related homologues, StarD5 and StarD6
The cholesterol-regulated StarD4 gene encodes a StAR-related lipid transfer protein with two closely related homologues, StarD5 and StarD6
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DOI：
10.1073/pnas.052143799
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发表时间：
2002-05-14
影响因子：
11.1
通讯作者：
Breslow, JL
中科院分区：
文献类型：
--
作者：
Soccio, RE;Adams, RM;Breslow, JL
使用cDNA微阵列，我们确定了StarD 4作为一个基因，其表达在高胆固醇饮食的小鼠肝脏中减少了2倍以上。StarD 4在培养的3 T3细胞中的表达也受到固醇调节，并且已知的固醇调节元件结合蛋白（SREBP）靶基因表现出协调调节。与StarD 4最接近的同源物是另外两种与StAR相关的脂质转移（START）蛋白，分别命名为StarD 5和StarD 6。StarD 4、StarD 5和StarD 6是几乎完全由START结构域组成的205- 233-aa蛋白。这三种蛋白组成了START蛋白的一个亚家族，彼此之间有大约30%的氨基酸同源性，与星星和MLN 64的胆固醇结合START结构域有大约20%的同源性，与磷脂酰胆碱转移蛋白（PCTP）和其他START结构域的同源性小于15%。StarD 4和StarD 5在大多数组织中表达，在肝脏和肾脏中表达水平最高，而StarD 6仅在睾丸中表达。与StarD 4相反，StarD 5和MLN 64的表达不受固醇调节。StarD 4、StarD 5和StarD 6可能参与固醇或其他脂质的细胞内转运。
Using cDNA microarrays, we identified StarD4 as a gene whose expression decreased more than 2-fold in the livers of mice fed a high-cholesterol diet. StarD4 expression in cultured 3T3 cells was also sterol-regulated, and known sterol regulatory element binding protein (SREBP)-target genes showed coordinate regulation. The closest homologues to StarD4 were two other StAR-related lipid transfer (START) proteins named StarD5 and StarD6. StarD4, StarD5, and StarD6 are 205- to 233-aa proteins consisting almost entirely of START domains. These three constitute a subfamily among START proteins, sharing approximate to30% amino acid identity with one another, approximate to20% identity with the cholesterol-binding START domains of StAR and MLN64, and less than 15% identity with phosphatidylcholine transfer protein (PCTP) and other START domains. StarD4 and StarD5 were expressed in most tissues, with highest levels in liver and kidney, whereas StarD6 was expressed exclusively in the testis. In contrast to StarD4, expression of StarD5 and MLN64 was not sterol-regulated. StarD4, StarD5, and StarD6 may be involved in the intracellular transport of sterols or other lipids.