Uridine Cytidine Kinase Like-1 Enhances Tumor Cell Proliferation and Mediates Protection from Natural Killer-Mediated Killing.
Uridine Cytidine Kinase Like-1 Enhances Tumor Cell Proliferation and Mediates Protection from Natural Killer-Mediated Killing.
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DOI：
10.23937/2378-3672/1410018
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发表时间：
2016-01-01
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影响因子：
--
通讯作者：
Kornbluth, Jacki
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作者：
Gullickson, Gail;Ambrose, Elise C;Kornbluth, Jacki
尿嘧啶胞苷激酶样-1 （UCKL-1）是一种在许多肿瘤细胞中过度表达的蛋白，在高度恶性、侵袭性肿瘤中尤其如此。序列分析表明UCKL-1与尿苷激酶具有同源性，尿苷激酶在DNA和RNA合成中起作用，在肿瘤细胞中经常上调。先前的研究表明UCKL-1是NK细胞溶解颗粒中发现的一种E3泛素连接酶NKLAM （natural killer lytic-associated molecule）的底物。NKLAM使UCKL-1泛素化导致其降解。NKLAM表达的增加增强了nk介导的肿瘤杀伤活性。UCKL-1是NKLAM的底物这一事实表明，UCKL-1可能在肿瘤细胞中提供NK杀伤的抗性。本研究表明，UCKL-1过表达可保护肿瘤细胞免受NK杀伤，并提高肿瘤在体内的存活率。UCKL-1也有更广泛的作用，保护肿瘤细胞免受自发和药物诱导的凋亡，增加肿瘤细胞的增殖。核因子κ B （nf - κ B）活性在转染UCKL-1的肿瘤细胞中高于转染对照细胞，这表明UCKL-1影响肿瘤生长和存活的至少一种可能机制。
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 in vivo. 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-kappaB) 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.