FHA domain of AGGF1 is essential for its nucleocytoplasmic transport and angiogenesis
Cui-Fang Zhang1, Han-Ming Wang1, Andong Wu2
1Department of Human Population Genetics, Institute of Molecular Medicine, Peking University, Beijing, 100871, China.
Abstract:
Angiogenic factor with G-patch and FHA domains 1 (AGGF1) exhibits a dynamic distribution from the nucleus to the cytoplasm in endothelial cells during angiogenesis, but the biological significance and underlying mechanism of this nucleocytoplasmic transport remains unknown. Here, we demonstrate that the dynamic distribution is essential for AGGF1 to execute its angiogenic function. To search the structural bases for this nucleocytoplasmic transport, we characterized three potential nuclear localization regions, one potential nuclear export region, forkhead-associated (FHA), and G-patch domains to determine their effects on nucleocytoplasmic transport and angiogenesis, and we show that AGGF1 remains intact during the dynamic subcellular distribution and the region from 260 to 288 amino acids acts as a signal for its nuclear localization. The distribution of AGGF1 in cytoplasm needs both FHA domain and 14-3-3α/β. Binding of AGGF1 via FHA domain to 14-3-3α/β is required to complete the transport. Thus, we for the first time established structural bases for the nucleocytoplasmic transport of AGGF1 and revealed that the FHA domain of AGGF1 is essential for its nucleocytoplasmic transport and angiogenesis.
Related Concept Videos
Regulation of Angiogenesis and Blood Supply
Intracellular Signaling Affects Focal Adhesions
Some...
Fibronectins Connect Cells with ECM
Both proteoglycans and collagen are attached to fibronectin proteins, which, in turn, are attached to integrin proteins. These integrin proteins interact with transmembrane...
Mechanism of Angiogenesis
Coat Assembly and GTPases
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
Rab Cascades


