Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
Trends Immunol. 2011 Aug;32(8):380-7. doi: 10.1016/j.it.2011.05.005. Epub 2011 Jul 13.
A disintegrin and metalloproteinase 17 (ADAM17), also known as tumor necrosis factor-α converting enzyme (TACE), is a membrane-bound enzyme that cleaves cell surface proteins, such as cytokines (e.g. TNFα), cytokine receptors (e.g. IL-6R and TNF-R), ligands of ErbB (e.g. TGFα and amphiregulin) and adhesion proteins (e.g. L-selectin and ICAM-1). Here we examine how ectodomain shedding of these molecules can alter their biology and impact on immune and inflammatory responses and cancer development. Gene targeting of Adam17 is embryonic lethal, highlighting the importance of ectodomain shedding during development. Tissue-specific deletion, or hypomorphic knock-in, of Adam17 demonstrates an in vivo role for ADAM17 in controlling inflammation and tissue regeneration. The potential of ADAM17 as therapeutic target is also discussed.
解整合素金属蛋白酶 17（ADAM17），也称为肿瘤坏死因子-α转化酶（TACE），是一种膜结合酶，可切割细胞表面蛋白，如细胞因子（例如 TNFα）、细胞因子受体（例如 IL-6R 和 TNF-R）、表皮生长因子受体（ErbB）的配体（例如 TGFα 和 Amphiregulin）和粘附蛋白（例如 L-选择素和 ICAM-1）。在这里，我们研究了这些分子的细胞外结构域脱落如何改变它们的生物学特性，并影响免疫和炎症反应以及癌症的发展。Adam17 的基因靶向是胚胎致死的，这突显了细胞外结构域脱落在发育过程中的重要性。Adam17 的组织特异性缺失或功能减弱的基因敲入表明 ADAM17 在控制炎症和组织再生方面具有体内作用。还讨论了 ADAM17 作为治疗靶标的潜力。
