Intracellular composition of fatty acid affects the processing and function of tyrosinase through the ubiquitin-proteasome pathway
Intracellular composition of fatty acid affects the processing and function of tyrosinase through the ubiquitin-proteasome pathway
复制标题
DOI：
10.1042/bj20051419
复制
发表时间：
2006-02-15
影响因子：
4.1
通讯作者：
Hearing, VJ
中科院分区：
文献类型：
--
作者：
Ando, H;Wen, ZM;Hearing, VJ
蛋白酶体是细胞内选择性降解泛素化蛋白的多催化蛋白酶复合物。我们最近已经证明，脂肪酸，细胞膜的主要成分，能够调节酪氨酸酶，黑色素生物合成所需的关键酶的蛋白酶体降解，在对比的方式由泛素化酪氨酸酶的相对增加或减少。在本研究中，我们表明，改变细胞内的脂肪酸组成的影响后高尔基体酪氨酸酶降解。用亚油酸（C-18：2）孵育显著改变了培养的B16黑素瘤细胞的脂肪酸组成，即多不饱和脂肪酸如亚油酸和花生四烯酸（C-20：4）的显著增加被单不饱和脂肪酸如油酸（C-18：1）和棕榈油酸（C-16：1）的减少所补偿，而对饱和脂肪酸与不饱和脂肪酸的比例几乎没有影响。当细胞内脂肪酸组成发生变化时，酪氨酸酶迅速从内质网进入高尔基体，并在高尔基体成熟后降解增加。在蛋白酶体抑制剂存在下用亚油酸处理细胞时，观察到酪氨酸酶在ER中的保留，这解释了尽管酪氨酸酶降解被消除，但用亚油酸和蛋白酶体抑制剂处理的细胞中黑色素合成减少的原因。这些结果表明，细胞内的脂肪酸组成影响酪氨酸酶的加工和功能与泛素-蛋白酶体途径，并建议这可能是一个常见的生理途径，以调节蛋白质降解。
Proteasomes are multicatalytic proteinase complexes within cells that selectively degrade ubiquitinated proteins. We have recently demonstrated that fatty acids, major components of cell membranes, are able to regulate the proteasomal degradation of tyrosinase, a critical enzyme required for melanin biosynthesis, in contrasting manners by relative increases or decreases in the ubiquitinated tyrosinase. In the present study, we show that altering the intracellular composition of fatty acids affects the post-Golgi degradation of tyrosinase. Incubation with linoleic acid (C-18:2) dramatically changed the fatty acid composition of cultured B16 melanoma cells, i.e. the remarkable increase in polyunsaturated fatty acids Such as linoleic acid and arachidonic acid (C-20:4) was compensated by the decrease in monounsaturated fatty acids such its oleic acid (C-18:1) and palmitoleic acid (C-16:1), with little effect on the proportion of saturated to unsaturated fatty acid. When the composition of intracellular fatty acids was altered, tyrosinase was rapidly processed to the Golgi apparatus from the ER (endoplasmic reticulum) and the degradation of tyrosinase was increased after its maturation in file Golgi. Retention of tyrosinase in the ER was observed when cells were treated with linoleic acid in the presence of proteasome inhibitors, explaining why melanin synthesis was decreased in cells treated with linoleic acid and a proteasome inhibitor despite the abrogation of tyrosinase degradation. These results suggest that the intracellular composition of fatty acid affects the processing and function of tyrosinase in connection with the ubiquitin-proteasome pathway and suggest that this might be a common physiological approach to regulate protein degradation.