Translational regulation of autoimmune inflammation and lymphoma genesis by programmed cell death 4
Translational regulation of autoimmune inflammation and lymphoma genesis by programmed cell death 4
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DOI：
10.4049/jimmunol.177.11.8095
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发表时间：
2006-12-01
影响因子：
4.4
通讯作者：
Chen, Youhai H.
中科院分区：
文献类型：
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作者：
Hilliard, Anja;Hilliard, Brendan;Chen, Youhai H.
炎症性疾病和癌症都与蛋白翻译升高有关。然而，这些疾病的翻译调控机制和翻译因子的作用尚不清楚。程序性细胞死亡4 （PDCD4）是一种新发现的蛋白质翻译抑制剂。为了确定PDCD4在体内的作用，我们通过基因靶向产生了PDCD4缺陷小鼠。我们在这里报道，缺乏PDCD4的小鼠会发生自发性淋巴瘤，并且寿命显著缩短。大多数肿瘤起源于B淋巴，常转移到肝脏和肾脏。然而，pdcd4缺陷小鼠对自身免疫性脑脊髓炎和糖尿病等炎症性疾病具有抵抗力。机制研究表明，激活后，pdcd4缺陷淋巴细胞优先产生促进肿瘤发生但抑制炎症的细胞因子。这些结果表明，PDCD4通过选择性抑制免疫系统中的蛋白质翻译来控制淋巴瘤的发生和自身免疫性炎症。
Both inflammatory diseases and cancer are associated with heightened protein translation. However, the mechanisms of translational regulation and the roles of translation factors in these diseases are not clear. Programmed cell death 4 (PDCD4) is a newly described inhibitor of protein translation. To determine the roles of PDCD4 in vivo, we generated PDCD4-deficient mice by gene targeting. We report here that mice deficient in PDCD4 develop spontaneous lymphomas and have a significantly reduced life span. Most tumors are of the B lymphoid origin with frequent metastasis to liver and kidney. However, PDCD4-deficient mice are resistant to inflammatory diseases such as autoimmune encephalomyelitis and diabetes. Mechanistic studies reveal that upon activation, PDCD4-deficient lymphocytes preferentially produce cytokines that promote oncogenesis but inhibit inflammation. These results establish that PDCD4 controls lymphoma genesis and autoimmune inflammation by selectively inhibiting protein translation in the immune system.