Cidea蛋白调节脂肪代谢,在机体能量平衡过程中起重要作用,在转录和翻译后水平受到严格调控,但在翻译水平的调节还不清楚.通过对CIDEA基因敲除小鼠模型研究,鉴定了小鼠棕色脂肪组织内源性表达Cidea蛋白N端缺失异构体mCidea-22.定点突变等研究表明其产生机制为选择性起始翻译.并且,在异位表达时,N端缺失异构体和全长异构体的比例呈现细胞系特异性.此外,蛋白质稳定性实验表明mCidea-22半衰期很短.亚细胞定位研究显示mCidea-22是内质网和脂滴定位蛋白.为深入理解Cidea蛋白的功能和精细调节提供了新的思路和方向.
Metabolic diseases including obesity and diabetes are emerging as major health threats over the world. Cidea, a member of CIDE family proteins, plays an important role in energy homeostasis in brown adipose tissue by regulating lipid storage and AMPK stability. Cidea is tightly regulated at both transcriptional and posttranslational levels, but little is known about its translational regulation. Here, a novel N-terminal truncated isoform of Cidea (mCidea-22) was identified in mouse brown adipose tissue. Using mutational analysis, it was demonstrated that this isoform was generated by alternative translation. Ectopic expression of mCidea cDNA in various cell lines showed that expression of mCidea-22 was cell type specific with its highest expression in preadipocyte 3T3-L1 cells. In addition, it was observed that mCidea-22 had a short half-life and was localized to ER and lipid droplets. Taken together, the data provide strong evidence that translational control played an important role in the regulation of Cidea expression.