Siri A, Knäuper V, Veirana N, Caocci F, Murphy G, Zardi L
Laboratory of Cell Biology, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
J Biol Chem. 1995 Apr 14;270(15):8650-4. doi: 10.1074/jbc.270.15.8650.
Two major tenascin-C (TN-C) isoforms are generated by the alternative splicing of the pre-mRNA. The large isoform contains seven extra type three repeats that, by contrast, are omitted in the small TN-C isoform. The large TN-C isoform is mainly expressed at the onset of cellular processes that entail active cell migration, proliferation, or tissue remodeling such as occur in neoplasia, wound healing, and during development. Thus, the large TN-C isoform seems to be a specific component of the provisional extracellular matrix. Here we have studied the degradation of the large and small TN-C isoforms by matrix metalloproteinases (MMPs) 2, 3, 7, and 9. Among these proteolytic enzymes only MMP-7 can degrade the small TN-C isoform removing the NH2-terminal knob. The large TN-C isoform shows the same MMP-7-sensitive site adjacent to the NH2-terminal sequence, but is further degraded in the splicing area where three fibronectin-like type III repeats are completely digested. Moreover, the large TN-C isoform is degraded by MMP-2 and MMP-3 which completely digest a single type III repeat inside the splicing area. By contrast, the large TN-C isoform is resistant to MMP-9 digestion. The results show that the presence of the spliced sequence introduces new protease-sensitive sites in the large TN-C isoform.
两种主要的腱生蛋白-C（TN-C）同工型是由前体mRNA的可变剪接产生的。大的同工型包含七个额外的III型重复序列，相比之下，小的TN-C同工型则没有这些序列。大的TN-C同工型主要在涉及活跃细胞迁移、增殖或组织重塑的细胞过程开始时表达，例如在肿瘤形成、伤口愈合以及发育过程中。因此，大的TN-C同工型似乎是临时细胞外基质的一个特定成分。在这里，我们研究了基质金属蛋白酶（MMP）2、3、7和9对大、小TN-C同工型的降解作用。在这些蛋白水解酶中，只有MMP-7能够降解小的TN-C同工型并去除其NH2末端的球状结构。大的TN-C同工型在与NH2末端序列相邻处显示出相同的MMP-7敏感位点，但在剪接区域会进一步降解，其中三个纤连蛋白样III型重复序列会被完全消化。此外，大的TN-C同工型会被MMP-2和MMP-3降解，它们会完全消化剪接区域内的一个III型重复序列。相比之下，大的TN-C同工型对MMP-9的消化具有抗性。结果表明，剪接序列的存在为大的TN-C同工型引入了新的蛋白酶敏感位点。
