Mater Research Institute - The University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, Qld 4102, Australia.
Biol Chem. 2018 Sep 25;399(9):1091-1097. doi: 10.1515/hsz-2017-0308.
The cellular receptor CUB domain containing protein 1 (CDCP1) is commonly elevated and functionally important in a range of cancers. CDCP1 is cleaved by serine proteases at adjacent sites, arginine 368 (R368) and lysine 369 (K369), which induces cell migration in vitro and metastasis in vivo. We demonstrate that membrane localization of serine protease activity increases efficacy of cleavage of CDCP1, and that both secreted and membrane anchored serine proteases can have distinct preferences for cleaving at CDCP1-R368 and CDCP1-K369. Approaches that disrupt membrane localization of CDCP1 cleaving serine proteases may interfere with the cancer promoting effects of CDCP1 proteolysis.
细胞表面受体含 CUB 结构域蛋白 1（CDCP1）在多种癌症中普遍升高且具有重要的功能。丝氨酸蛋白酶在毗邻位点精氨酸 368（R368）和赖氨酸 369（K369）处切割 CDCP1，诱导体外细胞迁移和体内转移。我们证明，丝氨酸蛋白酶活性的膜定位增加了 CDCP1 切割的效力，并且分泌的和膜锚定的丝氨酸蛋白酶都可以对 CDCP1-R368 和 CDCP1-K369 的切割具有不同的偏好。破坏 CDCP1 切割丝氨酸蛋白酶膜定位的方法可能会干扰 CDCP1 蛋白水解的促进癌症的作用。
