β3-Endonexin interacts with ninein in vascular endothelial cells to promote angiogenesis.

Anti-angiogenesis serves as an effective tumor therapy approach. In a previous study, we found that β3-endonexin expressed in vascular endothelial cells was involved in promoting proliferation and angiogenesis partially by facilitating VEGF expression. However, it still remains unclear if β3-endonexin in vascular endothelial cells also employs other mechanisms in regulating angiogenesis. In this study, we utilized a β3-endonexin mutant (M2) carrying a defective nuclear localization sequence to disrupt its nuclear localization and evaluated its ability to promote HUVEC proliferation and formation of tube-like vascular structures. In addition, we performed yeast 2-hybrid assay to identify potential functional effectors of β3-endonexin. We found that both wild type β3-endonexin and the M2 mutant could localize to centrosomes in HUVECs and both were able to promote HUVEC proliferation and formation of vascular structures. However, the M2 mutant failed to promote VEGF expression in HUVECs. Further, we found that both wild type β3-endonexin and the M2 mutant were capable of binding to ninein, a centrosomal protein with a proangiogenic effect. Knockdown of ninein in HUVECs impeded centrosome localization of wild type β3-endonexin and the M2 mutant and inhibited HUVEC proliferation and formation of vascular structures. Taken together, these findings suggest that β3-endonexin interacts with centrosome ninein and contributes to HUVEC proliferation and formation of vascular structures.