Cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) is overexpressed and has an oncogenic role in hepatocellular carcinoma (HCC). Interleukin enhancer binding factor 2 (ILF2) has become research hotspot in liver cancer recently. However, it is still unclear whether and how CREB and ILF2 interact with each other. And how this interaction exerts its role in occurrence and development of liver cancer is still unclear. Here, we found that ILF2 directly bound with CREB, and this binding was essential for the malignant phenotypes of liver cancer cells. Moreover, we found that ILF2 acted as one of the upstream proteins of CREB and promoted CREB only in the protein level, whereas ILF2 expression was not regulated by CREB. Mechanistically, ILF2 bound to the pKID domain of CREB and stimulated its phosphorylation at Ser133. Taken together, our study finds a novel interaction between CREB and ILF2 in liver cancer, and this interaction might play a role in the diagnosis and remedy of liver cancer.

中文翻译：

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ILF2直接结合并稳定CREB以刺激肝癌细胞的恶性表型。

环状单磷酸腺苷（cAMP）反应元件结合蛋白（CREB）过度表达，在肝细胞癌（HCC）中具有致癌作用。白介素增强子结合因子2（ILF2）已成为肝癌的研究热点。但是，目前还不清楚CREB和ILF2是否以及如何相互作用。尚不清楚这种相互作用如何在肝癌的发生和发展中发挥作用。在这里，我们发现ILF2直接与CREB结合，这种结合对于肝癌细胞的恶性表型至关重要。此外，我们发现ILF2充当CREB的上游蛋白之一，仅在蛋白水平上促进CREB，而ILF2的表达不受CREB的调节。从机制上讲，ILF2与CREB的pKID域结合并刺激其在Ser133的磷酸化。