抑制素结合蛋白与母源性胚胎亮氨酸拉链激酶相互作用
Arrestin-3 interaction with maternal embryonic leucine-zipper kinase.
机构信息
Department of Pharmacology, Vanderbilt University, Nashville, TN 37232-0146, USA.
Division of Chemical Biology & Medicinal Chemistry, The University of Texas at Austin, Austin, TX 78712, USA; Medicinal Chemistry Department, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
出版信息
Cell Signal. 2019 Nov;63:109366. doi: 10.1016/j.cellsig.2019.109366. Epub 2019 Jul 25.
Maternal embryonic leucine-zipper kinase (MELK) overexpression impacts survival and proliferation of multiple cancer types, most notably glioblastomas and breast cancer. This makes MELK an attractive molecular target for cancer therapy. Yet the molecular mechanisms underlying the involvement of MELK in tumorigenic processes are unknown. MELK participates in numerous protein-protein interactions that affect cell cycle, proliferation, apoptosis, and embryonic development. Here we used both in vitro and in-cell assays to identify a direct interaction between MELK and arrestin-3. A part of this interaction involves the MELK kinase domain, and we further show that the interaction between the MELK kinase domain and arrestin-3 decreases the number of cells in S-phase, as compared to cells expressing the MELK kinase domain alone. Thus, we describe a new mechanism of regulation of MELK function, which may contribute to the control of cell fate.
母源胚胎亮氨酸拉链激酶（MELK）过表达影响多种癌症类型的存活和增殖，尤其是神经胶质瘤和乳腺癌。这使得 MELK 成为癌症治疗的一个有吸引力的分子靶点。然而，MELK 参与肿瘤发生过程的分子机制尚不清楚。MELK 参与了许多影响细胞周期、增殖、凋亡和胚胎发育的蛋白质-蛋白质相互作用。在这里，我们使用体外和细胞内测定法来鉴定 MELK 和 arrestin-3 之间的直接相互作用。该相互作用的一部分涉及 MELK 激酶结构域，我们进一步表明，与单独表达 MELK 激酶结构域的细胞相比，MELK 激酶结构域与 arrestin-3 之间的相互作用减少了 S 期细胞的数量。因此，我们描述了 MELK 功能调控的新机制，这可能有助于控制细胞命运。
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