E235 is an ATF4 Expression Regulator for Tumor Research
Activates transcription factor 4 (ATF4) is a cAMP-responsive element binding protein, belonging to the cAMP-responsive element binding protein (CREB)-2 protein family. This protein is divided into several structural domains that are crucial for the function and degradation of ATF4. Specifically, ATF4 is a stress-induced transcription factor that is frequently upregulated in cancer cells. Besides, ATF4 controls the expression of a wide range of adaptive genes. Moreover, ATF4 itself is not a functional transcription factor, but rather half of many possible heterodimer transcription factors. Furthermore, ATF4 can participate in multiple different heterodimers simultaneously.
In cells, ATF4 controls multiple signaling pathways, including autophagy, oxidative stress, inflammation, and translation. This indicates that ATF4 has multiple roles in various pathological progression. However, ATF4 can trigger pro-survival and pro-death pathways. Meanwhile, ATF4 mRNA is generally transcribed at low levels. But its protein expression depends on various stress conditions such as hypoxia, hypoxia, nutritional deficiency, and glucose deprivation. Nonetheless, the ATF4 signal supports many normal biological processes, such as the maintenance or immune regulation of stem cells and progenitor cells. Under sustained stress conditions, ATF4 promotes the induction of cell apoptosis. Here, we will introduce an expression regulator of ATF4, E235.
E235 is an ATF4 Expression Regulator for Tumor Research.
At first, E235 reduces cell viability by activating integrated stress response (ISR) and DNA damage response signals. Importantly, E235 has anti-proliferative activity and has the potential for tumor research.
Secondly, E235 with 1 µM for 2-24 h down-regulates the level of XBP-1s mRNA in HT1080 cells in a time-dependent manner. Obviously, E235 has anti-proliferative activity on HT1080, RPMI-8226, B16F10, 4T1, HT1080 shNT and HT1080 shATF4 cells.
Thirdly, E235 increases the expression of p53 in a dose-dependent manner in AG1522 cells. E235 increases the expression of p-Chk2 in AG1522 cells. Particularly, E235 increases the expression of p-p53 in AG1522 and HT1080 cells. Additionally, E235 increases the expression of γ-H2AX in a dose-dependent manner in HT1080 cells.
Finally, E235 is an ATF4 expression regulator and has anti-proliferative activity, and has the potential for tumor research.