Rogers J T
Division of Hematology/Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 USA.
Blood. 1996 Mar 15;87(6):2525-37.
Interleukin-1beta (IL-1beta) elevates H- and L-ferritin subunit synthesis in both human hepatoma cells (HepG2) and primary human umbilical vein endothelial cells. Ferritin induction is greater than the increase in total HepG2 protein synthesis in response to IL-1. IL-6 causes a moderate increase in L-subunit synthesis. The levels of the mRNAs for the ferritin H-subunits (H-mRNA) and light subunits (L-mRNA) remain unchanged, indicating that expression of the iron storage protein, ferritin, is regulated by translational mechanisms during inflammation. We have found a translational enhancer region in the L-ferritin mRNA 5'UTR that confers two-fold baseline and twofold IL-1-dependent translational regulation to a CAT reporter message. The L-mRNA motif is related to a 61 nucleotide (nt) G+C-rich translational enhancer within 70 nt of the H-ferritin start codon. Sequences upstream of the start codons (SUS elements) in both H-mRNA and L-mRNAs confer IL-1beta but not IL-6-dependent translation to hybrid ferritin/CAT reporter mRNAs. The H- and L-ferritin mRNA SUS elements contain a motif similar to a consensus reported for the 5' leaders of other acute phase response mRNAs. Transfected hybrid H-mRNA SUS/CAT mRNAs with a three nucleotide deleted version of the H-mRNA SUS displays an eightfold reduced level of translation and no longer confer IL-1beta-dependent translation.
白细胞介素-1β（IL-1β）可提高人肝癌细胞（HepG2）和人脐静脉内皮细胞中H型和L型铁蛋白亚基的合成。铁蛋白的诱导作用大于IL-1刺激下HepG2细胞总蛋白合成的增加。IL-6可使L亚基合成适度增加。铁蛋白H亚基（H-mRNA）和轻亚基（L-mRNA）的mRNA水平保持不变，这表明在炎症过程中，铁储存蛋白铁蛋白的表达受翻译机制调控。我们在L-铁蛋白mRNA 5'非翻译区发现了一个翻译增强子区域，它赋予氯霉素乙酰转移酶（CAT）报告基因信息两倍的基础翻译调控和两倍的IL-1依赖性翻译调控。L-mRNA基序与H-铁蛋白起始密码子70个核苷酸内的一个61个核苷酸（nt）富含G+C的翻译增强子相关。H-mRNA和L-mRNA起始密码子上游的序列（SUS元件）赋予铁蛋白/CAT报告基因杂合mRNA IL-1β依赖性翻译，但不赋予IL-6依赖性翻译。H型和L型铁蛋白mRNA SUS元件包含一个与其他急性期反应mRNA 5'前导序列报道的共有序列相似的基序。转染的具有H-mRNA SUS三核苷酸缺失版本的杂合H-mRNA SUS/CAT mRNA显示翻译水平降低了八倍，并且不再赋予IL-1β依赖性翻译。
