Guanylate-binding protein 1 modulates proteasomal machinery in ovarian cancer

Guanylate-binding protein 1 (GBP1) is known as an interferon -g -induced GTPase. Here, we used genetically modified ovarian cancer (OC) cells to study the role of GBP1. The data generated show that GBP1 inhibition constrains the clonogenic potential of cancer cells. In vivo studies revealed that GBP1 overexpression in tumors promotes tumor progression and reduces median survival, whereas GBP1 inhibition delayed tumor progression with longer median survival. We employed proteomics-based thermal stability assay (CETSA) on GBP1 knockdown and overexpressed OC cells to study its molecular functions. CETSA results show that GBP1 interacts with many members of the proteasome. Furthermore, GBP1 inhibition sensitizes OC cells to paclitaxel treatment via accumulated ubiquitinylated proteins where GBP1 inhibition decreases the overall proteasomal activity. In contrast, GBP1-overexpressing cells acquired paclitaxel resistance via boosted cellular proteasomal activity. Overall, these studies expand the role of GBP1 in the activation of proteasomal machinery to acquire chemoresistance.

Automated summary

GBP1 plays an important role in ovarian cancer cells, and its inhibition can limit the clonogenic potential of cancer cells. In addition, GBP1 overexpression promotes tumor progression and decreases median survival, while GBP1 inhibition delays tumor progression and increases median survival. Furthermore, GBP1 interacts with multiple members of the proteasome, affecting the sensitivity of OC cells to paclitaxel treatment by controlling proteasomal activity.