Gullickson Gail, Ambrose Elise C, Hoover Richard G, Kornbluth Jacki
Department of Pathology, Saint Louis University School of Medicine, USA.
VA, St. Louis Health Care System, St. Louis, USA.
Int J Immunol Immunother. 2016;3(1). doi: 10.23937/2378-3672/1410018. Epub 2016 May 24.
Uridine cytidine kinase like-1 (UCKL-1) is a largely uncharacterized protein over-expressed in many tumor cells, especially in highly malignant, aggressive tumors. Sequence analysis indicates that UCKL-1 has homology to uridine kinases, enzymes that play a role in DNA and RNA synthesis and that are often up-regulated in tumor cells. Previous studies have shown that UCKL-1 is a substrate for natural killer lytic-associated molecule (NKLAM), an E3 ubiquitin ligase found in NK cell cytolytic granules. Ubiquitination of UCKL-1 by NKLAM leads to its degradation. Increased expression of NKLAM enhances NK-mediated tumoricidal activity. The fact that UCKL-1 is a substrate for NKLAM suggests that UCKL-1 may provide resistance to NK killing in tumor cells. Here we show that UCKL-1 over-expression protects tumor cells from NK killing and enhances tumor survival . UCKL-1 also has a much broader role, protecting tumor cells from spontaneous and drug-induced apoptosis and increasing tumor cell proliferation. Nuclear factor-kappa B (NF-κB) activity is higher in tumor cells transfected with UCKL-1 compared to control transfected cells, suggesting at least one possible mechanism by which UCKL-1 influences tumor growth and survival.
尿苷胞苷激酶样-1（UCKL-1）是一种在很大程度上未被充分研究的蛋白质，在许多肿瘤细胞中过度表达，尤其是在高度恶性、侵袭性强的肿瘤中。序列分析表明，UCKL-1与尿苷激酶具有同源性，尿苷激酶是在DNA和RNA合成中发挥作用且在肿瘤细胞中常被上调的酶。先前的研究表明，UCKL-1是自然杀伤细胞溶解相关分子（NKLAM）的底物，NKLAM是一种存在于NK细胞溶细胞颗粒中的E3泛素连接酶。NKLAM对UCKL-1的泛素化导致其降解。NKLAM表达的增加增强了NK介导的杀瘤活性。UCKL-1是NKLAM的底物这一事实表明，UCKL-1可能为肿瘤细胞提供对NK杀伤的抗性。在此我们表明，UCKL-1的过表达可保护肿瘤细胞免受NK杀伤并提高肿瘤存活率。UCKL-1还具有更广泛的作用，保护肿瘤细胞免受自发和药物诱导的凋亡并增加肿瘤细胞增殖。与对照转染细胞相比，转染UCKL-1的肿瘤细胞中核因子-κB（NF-κB）活性更高，这表明UCKL-1影响肿瘤生长和存活的至少一种可能机制。
