Heterogeneous ribonuclear protein A18 (hnRNP A18) is an RNA binding protein (RBP) involved in the hypoxic cellular stress response and regulation of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression in melanoma, breast cancer, prostate cancer, and colon cancer solid tumors. hnRNP A18 is comprised of an N-terminal structured RNA recognition motif (RMM) and a C-terminal intrinsically disordered domain (IDD). Upon cellar stressors, such as UV and hypoxia, hnRNP A18 is phosphorylated by casein kinase 2 (CK2) and glycogen synthase kinase 3β (GSK-3β). After phosphorylation, hnRNP A18 translocates from the nucleus to the cytosol where it interacts with pro-survival mRNA transcripts for proteins such as hypoxia inducible factor 1α and CTLA-4. Both the hypoxic cellular response and modulation of immune checkpoints by cancer cells promote chemoradiation resistance and metastasis. In this study, the ¹ H, ¹³ C, and ¹⁵ N backbone and sidechain resonances of the 172 amino acid hnRNP A18 were assigned sequence-specifically and provide a framework for future NMR-based drug discovery studies toward targeting hnRNP A18. These data will also enable the investigation of the dynamic structural changes within the IDD of hnRNP A18 upon phosphorylation by CK2 and GSK-3β to provide critical insight into the structure and function of IDDs.

异质核糖核蛋白 A18 (hnRNP A18) 是一种 RNA 结合蛋白 (RBP)，参与黑色素瘤、乳腺癌、前列腺癌和细胞毒性 T 淋巴细胞相关蛋白 4 (CTLA-4) 表达的缺氧细胞应激反应和调节结肠癌实体瘤。hnRNP A18 由一个 N 端结构化 RNA 识别基序 (RMM) 和一个 C 端固有无序结构域 (IDD) 组成。在地窖应激源（例如紫外线和缺氧）下，hnRNP A18 被酪蛋白激酶 2 (CK2) 和糖原合酶激酶 3β (GSK-3β) 磷酸化。磷酸化后，hnRNP A18 从细胞核易位到胞质溶胶，在那里它与蛋白质（如缺氧诱导因子 1α 和 CTLA-4）的促存活 mRNA 转录物相互作用。癌细胞的缺氧细胞反应和免疫检查点的调节都会促进放化疗抵抗和转移。在这项研究中， 172 个氨基酸的 hnRNP A18 的 1 H、 13 C 和 15 N 主链和侧链共振被特定序列分配，并为未来基于 NMR 的药物发现研究提供了一个框架，^以 靶向^hnRNP  A18 ^。这些数据还将有助于研究 hnRNP A18 在 CK2 和 GSK-3β 磷酸化后 IDD 内的动态结构变化，从而提供对 IDD 结构和功能的重要洞察。