{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Angiogenic factor with G‐patch and FHA domains 1 (AGGF1) is emerging as a multifunctional regulator of vascular homeostasis and remodeling that participates in both physiological and pathological angiogenesis. AGGF1 potently promotes blood vessel formation and protects against ischemic injury by activating intracellular signaling cascades—including PI3K/AKT, ERK, and JNK pathways—and by modulating autophagy in endothelial cells, thereby enhancing cell proliferation, migration, and capillary tube formation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Transcriptional regulation of AGGF1 by factors such as GATA1 and its genetic variants have been implicated in congenital vascular malformations, including Klippel–Trenaunay syndrome, underscoring its pivotal role in vascular morphogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In various malignancies, including hepatocellular and esophageal cancers, aberrant overexpression of AGGF1 has been correlated with enhanced tumor angiogenesis, increased invasion, poor differentiation, and adverse clinical outcomes. In these contexts, AGGF1 functions not only through the activation of oncogenic pathways such as AKT/mTOR but also by modulating the tumor microenvironment and even influencing DNA damage repair and chemoresistance in colon cancer cells."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n At the subcellular level, AGGF1’s functionality is refined by its nucleocytoplasmic dynamics and its post‐transcriptional cross‐talk. Its FHA domain not only drives nuclear–cytoplasmic transport in concert with 14–3–3 proteins but also mediates interactions that ultimately influence autophagy—such as phosphorylation of ATG16L1 and modulation via its 3′ untranslated region that affects cardioprotective Mcl1 expression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "14"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, AGGF1 contributes to vascular integrity and injury repair by regulating vascular smooth muscle cell phenotype and neointimal formation through its interactions with integrins and myocardin‐related signaling; this is further expanded by studies showing its involvement in vascular inflammation and remodeling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "17"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n AGGF1 also plays crucial roles in specialized vascular beds. In retinal endothelial cells, for instance, its regulation of autophagy under conditions of hypoxia or hyperoxia modulates angiogenesis, while in the placenta, reduced AGGF1 expression has been linked with preeclampsia. Moreover, emerging data implicate AGGF1 in other disease processes such as hepatic steatosis and even in determining vascular parameters in aggressive brain tumors."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "18", "end_ref": "22"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, recent structural insights—such as the identification of an OCRE domain shared between AGGF1 and RNA‐binding proteins—provide clues to novel roles in RNA metabolism and additional signaling contexts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "23"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies reveal that AGGF1 is a versatile and vital mediator of angiogenesis, vascular differentiation, and tissue repair. Its diverse functional roles—as a modulator of autophagy, inflammation, cellular proliferation, and even DNA repair—underscore its potential as a diagnostic biomarker and as a therapeutic target in cardiovascular, oncologic, and metabolic diseases.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Qiulun Lu, Yufeng Yao, Zhenkun Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Angiogenic Factor AGGF1 Activates Autophagy with an Essential Role in Therapeutic Angiogenesis for Heart Disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Biol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pbio.1002529"}], "href": "https://doi.org/10.1371/journal.pbio.1002529"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27513923"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27513923"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yu Liu, Hui Yang, Lina Song, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AGGF1 protects from myocardial ischemia/reperfusion injury by regulating myocardial apoptosis and angiogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Apoptosis (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10495-014-1001-4"}], "href": "https://doi.org/10.1007/s10495-014-1001-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24893993"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24893993"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Teng Zhang, Yufeng Yao, Jingjing Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Haploinsufficiency of Klippel-Trenaunay syndrome gene Aggf1 inhibits developmental and pathological angiogenesis by inactivating PI3K and AKT and disrupts vascular integrity by activating VE-cadherin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddw273"}], "href": "https://doi.org/10.1093/hmg/ddw273"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27522498"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27522498"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Isabelle Callebaut, Jean-Paul Mornon "}, {"type": "b", "children": [{"type": "t", "text": "OCRE: a novel domain made of imperfect, aromatic-rich octamer repeats."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bioinformatics (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/bioinformatics/bti065"}], "href": "https://doi.org/10.1093/bioinformatics/bti065"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15486042"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15486042"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Chun Fan, Ping Ouyang, Ayse A Timur, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel roles of GATA1 in regulation of angiogenic factor AGGF1 and endothelial cell function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.036079"}], "href": "https://doi.org/10.1074/jbc.M109.036079"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19556247"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19556247"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Y Hu, L Li, S B Seidelmann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of association of common AGGF1 variants with susceptibility for Klippel-Trenaunay syndrome using the structure association program."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Hum Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1469-1809.2008.00458.x"}], "href": "https://doi.org/10.1111/j.1469-1809.2008.00458.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18564129"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18564129"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Wei Wang, Guang-Yao Li, Jian-Yu Zhu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of AGGF1 is correlated with angiogenesis and poor prognosis of hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Med Oncol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12032-015-0574-2"}], "href": "https://doi.org/10.1007/s12032-015-0574-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25796501"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25796501"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Wei Li, Qiang Fu, Wenling Man, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA OR3A4 participates in the angiogenesis of hepatocellular carcinoma through modulating AGGF1/akt/mTOR pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Pharmacol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ejphar.2019.01.049"}], "href": "https://doi.org/10.1016/j.ejphar.2019.01.049"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30710550"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30710550"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Li Ma, Ruixue Yang, Jingxiang Gu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The expression of AGGF1, FOXC2, and E-cadherin in esophageal carcinoma and their clinical significance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Medicine (Baltimore) (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/MD.0000000000022173"}], "href": "https://doi.org/10.1097/MD.0000000000022173"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32925786"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32925786"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Wensheng Wang, Guangxi Zhu, Shujie Lai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Angiogenic Factor with G Patch and FHA Domains 1 (AGGF1) Acts as Diagnostic Biomarker and Adverse Prognostic Factor of Hepatocellular Carcinoma (HCC): Evidence from Bioinformatic Analysis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Med Sci Monit (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.12659/MSM.919896"}], "href": "https://doi.org/10.12659/MSM.919896"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32090983"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32090983"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Nan Wang, Meilan Xu, Shuting Liao "}, {"type": "b", "children": [{"type": "t", "text": "[ole of AGGF1 in DNA damage repair and modulating chemotherapy resistance in human colon cancer cells "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "in vitro"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": "]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nan Fang Yi Ke Da Xue Xue Bao (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3969/j.issn.1673-4254.2018.07.15"}], "href": "https://doi.org/10.3969/j.issn.1673-4254.2018.07.15"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33168501"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33168501"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Xiaocheng Zhao, Pavel Nedvetsky, Fabio Stanchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endothelial PKA activity regulates angiogenesis by limiting autophagy through phosphorylation of ATG16L1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.46380"}], "href": "https://doi.org/10.7554/eLife.46380"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31580256"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31580256"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Lexi Ding, Shan Lu, Yu Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The 3' Untranslated Region Protects the Heart from Angiotensin II-Induced Cardiac Dysfunction via AGGF1 Expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Ther (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ymthe.2020.02.002"}], "href": "https://doi.org/10.1016/j.ymthe.2020.02.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32061268"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32061268"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Cui-Fang Zhang, Han-Ming Wang, Andong Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FHA domain of AGGF1 is essential for its nucleocytoplasmic transport and angiogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci China Life Sci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11427-020-1844-0"}], "href": "https://doi.org/10.1007/s11427-020-1844-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33471274"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33471274"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Yufeng Yao, Zhenkun Hu, Jian Ye, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeting AGGF1 (angiogenic factor with G patch and FHA domains 1) for Blocking Neointimal Formation After Vascular Injury."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Am Heart Assoc (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/JAHA.117.005889"}], "href": "https://doi.org/10.1161/JAHA.117.005889"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28649088"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28649088"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Bisheng Zhou, Sheng Zeng, Nan Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Angiogenic Factor With G Patch and FHA Domains 1 Is a Novel Regulator of Vascular Injury."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arterioscler Thromb Vasc Biol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/ATVBAHA.117.308992"}], "href": "https://doi.org/10.1161/ATVBAHA.117.308992"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28153879"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28153879"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Wenxia Si, Bisheng Zhou, Wen Xie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Angiogenic factor AGGF1 acts as a tumor suppressor by modulating p53 post-transcriptional modifications and stability via MDM2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2020.10.014"}], "href": "https://doi.org/10.1016/j.canlet.2020.10.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33069768"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33069768"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Rong Li, Guomin Yao, Lingxiao Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Autophagy is required for the promoting effect of angiogenic factor with G patch domain and forkhead-associated domain 1 (AGGF1) in retinal angiogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Microvasc Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mvr.2021.104230"}], "href": "https://doi.org/10.1016/j.mvr.2021.104230"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34339727"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34339727"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Guomin Yao, Rong Li, Junhui Du, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Angiogenic factor with G patch and FHA domains 1 protects retinal vascular endothelial cells under hyperoxia by inhibiting autophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biochem Mol Toxicol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jbt.22572"}], "href": "https://doi.org/10.1002/jbt.22572"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32633013"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32633013"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Jing Shao, Sheng Zeng, Bisheng Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Angiogenic factor with G patch and FHA domains 1 (Aggf1) promotes hepatic steatosis in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2016.10.071"}], "href": "https://doi.org/10.1016/j.bbrc.2016.10.071"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27865839"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27865839"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Lan-Fen An, Shu-Qi Chi, Jun Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of angiogenic factor with G patch and FHA domains 1 (AGGF1) in placenta from patients with preeclampsia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Folia Histochem Cytobiol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.5603/FHC.a2020.0016"}], "href": "https://doi.org/10.5603/FHC.a2020.0016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32602552"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32602552"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Eric M Thompson, Stephen T Keir, Talaignair Venkatraman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The role of angiogenesis in Group 3 medulloblastoma pathogenesis and survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuro Oncol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/neuonc/nox033"}], "href": "https://doi.org/10.1093/neuonc/nox033"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28379574"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28379574"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Yufeng Yao, Yong Li, Qixue Song, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Angiogenic Factor AGGF1-Primed Endothelial Progenitor Cells Repair Vascular Defect in Diabetic Mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/db18-1178"}], "href": "https://doi.org/10.2337/db18-1178"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31092480"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31092480"}]}]}]}