Sisto Margherita, Lisi Sabrina
Department of Translational Biomedicine and Neuroscience (DiBraiN), Section of Human Anatomy and Histology, University of Bari "Aldo Moro", Piazza Giulio Cesare 1, I-70124 Bari, Italy.
Cells. 2024 Dec 18;13(24):2092. doi: 10.3390/cells13242092.
ADAM17 is a member of the disintegrin and metalloproteinase (ADAM) family of transmembrane proteases with immunoregulatory activity in multiple signaling pathways. The functional ADAM17 is involved in the shedding of the ectodomain characterizing many substrates belonging to growth factors, cytokines, receptors, and adhesion molecules. The ADAM17-dependent pathways are known to be crucial in tumor development and progression and in the modulation of many pathological and physiological processes. In the last decade, ADAM17 was considered the driver of several autoimmune pathologies, and numerous substrate-mediated signal transduction pathways were identified. However, the discoveries made to date have led researchers to try to clarify the multiple mechanisms in which ADAM17 is involved and to identify any molecular gaps between the different transductional cascades. In this review, we summarize the most recent updates on the multiple regulatory activities of ADAM17, focusing on reported data in the field of autoimmunity.
ADAM17是跨膜蛋白酶解整合素和金属蛋白酶(ADAM)家族的成员,在多种信号通路中具有免疫调节活性。功能性ADAM17参与许多属于生长因子、细胞因子、受体和粘附分子的底物的胞外域脱落。已知ADAM17依赖性途径在肿瘤发生和发展以及许多病理和生理过程的调节中至关重要。在过去十年中,ADAM17被认为是几种自身免疫性疾病的驱动因素,并且鉴定了许多底物介导的信号转导途径。然而,迄今为止的发现促使研究人员试图阐明ADAM17所涉及的多种机制,并确定不同转导级联之间的任何分子间隙。在本综述中,我们总结了ADAM17多种调节活性的最新进展,重点关注自身免疫领域的报道数据。