Proszkowiec-Weglarz Monika, Humphrey Brooke D, Richards Mark P
Animal Biosciences and Biotechnology Laboratory, United States Department of Agriculture, Agricultural Research Service, Animal and Natural Resources Institute, Beltsville, MD 20705-2350, USA.
Mol Cell Biochem. 2008 May;312(1-2):167-84. doi: 10.1007/s11010-008-9732-6. Epub 2008 Mar 29.
Carbohydrate response element binding protein (ChREBP) and sterol regulatory element binding protein-1c (SREBP-1c) are transcription factors that are known to be key regulators of glucose metabolism and lipid synthesis in mammals. Since ChREBP and its co-activator Max-like protein X (Mlx) have not been identified in birds, the objectives of this work were to clone, sequence, and characterize the genomic organization of ChREBP and Mlx genes and to determine the expression of ChREBP, Mlx, and several related genes including liver X receptor (LXR), SREBP-1 and thyroid hormone responsive Spot 14 (Spot 14) in chickens. Alternative splicing resulted in two ChREBP mRNA transcript variants that code for predicted proteins of 895 and 869 amino acids. The chicken Mlx gene produced a single mRNA transcript that codes for a predicted protein of 245 amino acids. Chicken ChREBP and Mlx predicted proteins shared high amino acid homology with select portions of corresponding mammalian proteins. In chickens, Mlx, SREBP-1, and LXR were expressed at comparable levels in all tissues examined. However, ChREBP demonstrated significant tissue-specific expression with the highest mRNA levels found in liver and duodenum and Spot 14 was expressed predominantly in liver and abdominal fat. Using Western blotting, the presence of ChREBP protein was detected in chicken liver tissue. Our findings add new insight into a potential role for specific transcription factors such as ChREBP and Mlx in the glucose-dependent regulation of lipogenesis in birds.
碳水化合物反应元件结合蛋白(ChREBP)和固醇调节元件结合蛋白-1c(SREBP-1c)是转录因子,已知它们是哺乳动物葡萄糖代谢和脂质合成的关键调节因子。由于尚未在鸟类中鉴定出ChREBP及其共激活因子Max样蛋白X(Mlx),因此本研究的目的是克隆、测序和表征ChREBP和Mlx基因的基因组结构,并确定ChREBP、Mlx以及包括肝脏X受体(LXR)、SREBP-1和甲状腺激素反应性Spot 14(Spot 14)在内的几个相关基因在鸡中的表达情况。可变剪接产生了两种ChREBP mRNA转录变体,它们编码预测的895和869个氨基酸的蛋白质。鸡Mlx基因产生了一种单一的mRNA转录本,编码一个预测的245个氨基酸的蛋白质。鸡ChREBP和Mlx预测的蛋白质与相应哺乳动物蛋白质的特定部分具有高度的氨基酸同源性。在鸡中,Mlx、SREBP-1和LXR在所有检测的组织中表达水平相当。然而ChREBP表现出显著的组织特异性表达,在肝脏和十二指肠中mRNA水平最高,而Spot 14主要在肝脏和腹部脂肪中表达。通过蛋白质免疫印迹法在鸡肝脏组织中检测到了ChREBP蛋白 的存在。我们的研究结果为ChREBP和Mlx等特定转录因子在鸟类脂肪生成的葡萄糖依赖性调节中的潜在作用提供了新的见解。