FHA domain of AGGF1 is essential for its nucleocytoplasmic transport and angiogenesis  

作　　者：Cui-Fang Zhang Han-Ming Wang Andong Wu Yang Li Xiao-Li Tian 

机构地区：[1]Department of Human Population Genetics,Institute of Molecular Medicine,Peking University,Beijing 100871,China [2]Aging and Vascular Diseases,Human Aging Research Institute and School of Life Science,Nanchang University,and Jiangxi Key Laboratory of Human Aging,Nanchang 330031,China

出　　处：《Science China(Life Sciences)》2021年第11期1884-1894,共11页中国科学（生命科学英文版）

基　　金：This work was supported by grants from the National Natural Science Foundation of China(30730047,81070262,81130003 and 81630034).

摘　　要：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.

关 键 词：AGGF1 nucleocytoplasmic transport ANGIOGENESIS FHA domain 14-3-3α/β 

分 类 号：Q75[生物学—分子生物学]