Novel negative regulator of expression in Fas ligand (CD178) cytoplasmic tail: Evidence for translational regulation and against Fas ligand retention in secretory lysosomes
Novel negative regulator of expression in Fas ligand (CD178) cytoplasmic tail: Evidence for translational regulation and against Fas ligand retention in secretory lysosomes
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DOI：
10.4049/jimmunol.173.8.5095
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发表时间：
2004-10-15
影响因子：
4.4
通讯作者：
Ju, ST
中科院分区：
文献类型：
--
作者：
Xiao, S;Deshmukh, US;Ju, ST
Fas配体（（FasL）CD 178）是一种II型跨膜蛋白，可诱导表达Fas受体的细胞凋亡。它具有独特的80个氨基酸的胞质尾区（FasL（Cyt））。作为一种II型跨膜蛋白，FasL（Cyt）的早期合成可通过影响FasL的内质网转位和/或内质网滞留来影响FasL的翻译。以往的研究表明，FasL（PRD）中富含脯氨酸的结构域（a a 43-70）通过将FasL保留在分泌性溶酶体中来抑制FasL膜表达。该报告显示，FasL（Cyt）的as 2-33的缺失显著增加了总FasL水平和FasL细胞表面表达。尽管存在FasL（PRD），但这种FasL表达的负调节因子是显性的。此外，未观察到富含脯氨酸结构域的FasL在细胞质中的保留。此外，我们证明，FasL（细胞色素）调节FasL的表达，通过控制FasL的从头合成的速率。我们的研究证明了一种新的FasL表达的负调控因子在FasL（Cyt）区域及其作用机制。
Fas ligand ((FasL) CD178), a type II transmembrane protein, induces apoptosis of cells expressing the Fas receptor. It possesses a unique cytoplasmic tail (FasL(Cyt)) of 80 aa. As a type II transmembrane protein, the early synthesis of FasL(Cyt) could affect FasL translation by impacting FasL endoplasmic reticulum translocation and/or endoplasmic reticulum retention. Previous studies suggest that the proline-rich domain (a a 43-70) in FasL(Cyt) (FasL(PRD)) inhibits FasL membrane expression by retaining FasL in the secretory lysosomes. This report shows that deletion of as 2-33 of FasL(Cyt) dramatically increased total FasL levels and FasL cell surface expression. This negative regulator of FasL expression is dominant despite the presence of FasL(PRD). In addition, retention of proline-rich domain-containing FasL in the cytoplasm was not observed. Moreover, we demonstrated that FasL(Cyt) regulates FasL expression by controlling the rate of de novo synthesis of FasL. Our study demonstrated a novel negative regulator of FasL expression in the FasL(Cyt) region and its mechanism of action.