TIA1 interacts with annexin A7 in regulating vascular endothelial cell autophagy

T-cell intracellular antigen-1 (TIA1) is a DNA/RNA binding protein broadly expressed in eukaryotic cells, participating in multiple aspects of cellular metabolism. TIA1 phosphorylation was related with cell apoptosis and its RNA binding activity, however, the regulator and other functions of TIA1 phosphorylation were very little known. To find the modulator of TIA1 phosphorylation, we performed yeast two-hybrid screening and identified annexin A7 (ANXA7) as an interaction protein of TIA1. Recent study showed that a small molecule ABO could directly target ANXA7 and inhibit ANXA7 activity and its targets' phosphorylation. As a GTPase, ANXA7 was speculated to modulate TIA1 phosphorylation. Our results showed that ABO treatment promoted the interaction between TIA1 and ANXA7, and then greatly inhibited phosphorylation of TIA1 in HUVECs. Further results showed that ABO-increased interaction between ANXA7 and TIA1 significantly promoted the processing of a pro-autophagic factor FLJ11812 and the expression of ATG13. Moreover, we found that ABO increased TIA1 protein level, co-localization of ANXA7 and TIA1, and ATG13 expression in the aortic endothelium of apoE(-/-) mice. These data highlighted the new role of TIA1 phosphorylation in autophagy.