A new study from researchers at Northwestern University has uncovered an unexpected role for a protein called Exportin-1, also known as Xpo1 or Crm1, which could help improve future cancer treatments. Exportin-1 has traditionally been known for transporting molecules from the nucleus of a cell to the surrounding cytoplasm. However, scientists have now discovered that the protein also plays a major role in activating genes inside cells.
The researchers found that Exportin-1 helps connect transcription factors, which control gene activity, to structures called nuclear pore complexes located along the edge of the nucleus. This connection appears to strengthen gene activation and increase transcription, the process where genetic information is copied to produce proteins. The discovery also helps explain an observation scientists have made for years: active genes often move closer to the outer edge of the nucleus when they are turned on.
Cancer Treatment
The findings may be especially important in cancer research because Exportin-1 is often found in unusually high levels in leukemia and several other cancers. Scientists believe the protein’s ability to increase gene activity may contribute to uncontrolled cancer cell growth. Although medications that block Exportin-1 already exist, they can cause significant side effects because the protein is also essential for normal cell transport functions.
Researchers hope that understanding Exportin-1’s separate role in gene activation could lead to more precise cancer therapies in the future. Further studies will investigate whether the same process occurs in human cells and whether treatments can target cancer-related activity without harming healthy cellular functions.
Molecular Biosciences Professor Jason Brickner said, who led the study.
“The work provides a molecular explanation for a phenomenon I discovered 20 years ago—the movement of genes to the nuclear periphery when they are turned on.”
“Exportin-1 is overexpressed in many leukemias and cancers. Because it binds to the genome, it may alter transcription to promote oncogenesis,”
said Northwestern Ph.D. student and first author Tiffany Ge.
“Inhibitors of Exportin-1 are given to patients who fail to respond to first- or second-line chemotherapies. But these therapies are very toxic and have many side effects because they block all nuclear export, which is an essential function of cells.”
