Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Technion Integrated Cancer Center, Faculty of Medicine, Technion Institute of Technology, Haifa, Israel.
FEBS Lett. 2022 Jun;596(11):1468-1480. doi: 10.1002/1873-3468.14376. Epub 2022 May 20.
Arginyl-tRNA-protein transferase 1 (ATE1) catalyses N-terminal protein arginylation, a post-translational modification implicated in cell migration, invasion and the cellular stress response. Herein, we report that ATE1 is overexpressed in NRAS-mutant melanomas, while it is downregulated in BRAF-mutant melanomas. ATE1 expression was higher in metastatic tumours, compared with primary tumours. Consistent with these findings, ATE1 depletion reduced melanoma cell viability, migration and colony formation. Reduced ATE1 expression also affected cell responses to mTOR and MEK inhibitors and to serum deprivation. Among putative ATE1 substrates is the tumour suppressor AXIN1, pointing to the possibility that ATE1 may fine-tune AXIN1 function in melanoma. Our findings highlight an unexpected role for ATE1 in melanoma cell aggressiveness and suggest that ATE1 constitutes a potential new therapeutic target.
精氨酰-tRNA 蛋白转移酶 1（ATE1）催化 N 端蛋白精氨酰化，这是一种参与细胞迁移、侵袭和细胞应激反应的翻译后修饰。在此，我们报告 ATE1 在NRAS 突变型黑色素瘤中过表达，而在 BRAF 突变型黑色素瘤中下调。与原发性肿瘤相比，ATE1 在转移性肿瘤中的表达更高。这些发现一致表明，ATE1 缺失减少了黑色素瘤细胞的活力、迁移和集落形成。减少 ATE1 的表达也影响了细胞对 mTOR 和 MEK 抑制剂以及血清剥夺的反应。AXIN1 是潜在的 ATE1 底物之一，这表明 ATE1 可能在黑色素瘤中精细调节 AXIN1 的功能。我们的研究结果强调了 ATE1 在黑色素瘤细胞侵袭性中的意外作用，并表明 ATE1 可能是一个新的潜在治疗靶点。
