4ove | pdb_00004ove
X-ray Crystal Structure of Mouse Netrin-1
Structural highlights
FunctionNET1_MOUSE Netrins control guidance of CNS commissural axons and peripheral motor axons. Its association with either DCC or some UNC5 receptors will lead to axon attraction or repulsion, respectively. It also serve as a survival factor via its association with its receptors which prevent the initiation of apoptosis. Involved in colorectal tumorigenesis by regulating apoptosis (By similarity). Publication Abstract from PubMedNetrin-1 has been shown to be up-regulated in a fraction of human cancers as a mechanism to allow these tumors to escape the pro-apoptotic activity of some of its main dependence receptors, the UNC5 homologs (UNC5H). Here we identify the V-2 domain of netrin-1 to be important for its interaction with the Ig1/Ig2 domains of UNC5H2. We generate a humanized anti-netrin-1 antibody that disrupts the interaction between netrin-1 and UNC5H2 and triggers death of netrin-1-expressing tumor cells in vitro. We also present evidence that combining the anti-netrin-1 antibody with epidrugs such as decitabine could be effective in treating tumors showing no or modest netrin-1 expression. These results support that this antibody is a promising drug candidate. Structural Decoding of the Netrin-1/UNC5 Interaction and its Therapeutical Implications in Cancers.,Grandin M, Meier M, Delcros JG, Nikodemus D, Reuten R, Patel TR, Goldschneider D, Orriss G, Krahn N, Boussouar A, Abes R, Dean Y, Neves D, Bernet A, Depil S, Schneiders F, Poole K, Dante R, Koch M, Mehlen P, Stetefeld J Cancer Cell. 2016 Feb 8;29(2):173-85. doi: 10.1016/j.ccell.2016.01.001. PMID:26859457[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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