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PMID:29100074
Citation |
Yu, W, Goncalves, KA, Li, S, Kishikawa, H, Sun, G, Yang, H, Vanli, N, Wu, Y, Jiang, Y, Hu, MG, Friedel, RH and Hu, GF (2017) Plexin-B2 Mediates Physiologic and Pathologic Functions of Angiogenin. Cell 171:849-864.e25 |
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Abstract |
Angiogenin (ANG) is a secreted ribonuclease (RNase) with cell-type- and context-specific roles in growth, survival, and regeneration. Although these functions require receptor-mediated endocytosis and appropriate subcellular localization, the identity of the cell surface receptor remains undefined. Here, we show that plexin-B2 (PLXNB2) is the functional receptor for ANG in endothelial, cancer, neuronal, and normal hematopoietic and leukemic stem and progenitor cells. Mechanistically, PLXNB2 mediates intracellular RNA processing that contribute to cell growth, survival, and regenerative capabilities of ANG. Antibodies generated against the ANG-binding site on PLXNB2 restricts ANG activity in vitro and in vivo, resulting in inhibition of established xenograft tumors, ANG-induced neurogenesis and neuroprotection, levels of pro-self-renewal transcripts in hematopoietic and patient-derived leukemic stem and progenitor cells, and reduced progression of leukemia in vivo. PLXNB2 is therefore required for the physiological and pathological functions of ANG and has significant therapeutic potential in solid and hematopoietic cancers and neurodegenerative diseases. |
Links |
PubMed PMC5847377 Online version:10.1016/j.cell.2017.10.005 |
Keywords |
Animals; Breast Neoplasms/metabolism; Breast Neoplasms/pathology; Cell Proliferation; Female; Glioblastoma/metabolism; Glioblastoma/pathology; Hematopoietic Stem Cells/metabolism; Heterografts; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology; Male; Mice; Mice, Inbred C57BL; Neoplasm Transplantation; Nerve Tissue Proteins/antagonists & inhibitors; Nerve Tissue Proteins/metabolism; Neurogenesis; Ribonuclease, Pancreatic/chemistry; Ribonuclease, Pancreatic/metabolism |
Significance
Annotations
Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
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GO:0045727: positive regulation of translation |
ECO:0000315: |
P |
Fig 6C shows that knockdown of PLXNB2 in the mouse cell line MyePro results in a decrease in protein synthesis. |
complete | ||||
Notes
See also
References
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