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Adhesion G protein-coupled receptors (ADGRs) encompass 33 human transmembrane proteins with long N termini involved in cell-cell and cell-matrix interactions. We show the ADGRB1 gene, which encodes Brain-specific angiogenesis inhibitor 1 (BAI1), is epigenetically silenced in medulloblastomas (MBs) through a methyl-CpG binding protein MBD2-dependent mechanism. Knockout of Adgrb1 in mice augments proliferation of cerebellar granule neuron precursors, and leads to accelerated tumor growth in the Ptch1+/- transgenic MB mouse model. BAI1 prevents Mdm2-mediated p53 polyubiquitination, and its loss substantially reduces p53 levels. Reactivation of BAI1/p53 signaling axis by a brain-permeable MBD2 pathway inhibitor suppresses MB growth in vivo. Altogether, our data define BAI1's physiological role in tumorigenesis and directly couple an ADGR to cancer formation.
Pubmed ID: 29894688 RIS Download
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The objective of this human tissue repository is to systematically collect, store, and distribute brain and other tissues for research dedicated to the improved understanding, care, and treatment of individuals with developmental disorders. Brain sections are primarily frozen in isopentane / dry ice. Tissues are stored in 10% formalin and frozen at -85 degrees C. Of special interest are individuals with Down syndrome and other chromosomal defects, mitochondrial encephalopathies, phenylketonuria and other aminoacidopathies, maternal PKU, Rett syndrome, leukodystrophies, lysosomal disorders, dyslexia, autism, and other neurodevelopmental disorders. The brain and tissue banks have extensive experience in arranging for the rapid retrieval of tissue upon the death of individuals who die while at home, in hospitals or hospice care. As a special service, the brain and tissue banks are able to assist researchers who are working with patients who intend to donate tissues at the time of their death. Immediately after retrieval of the tissue, the brain and tissue banks will forward needed tissue to the referring investigators and ensure proper storage and cataloging of any additional tissues as part of the brain and tissue banks. The recipient of tissue and the brain and tissue banks are required to sign a Tissue Transfer Agreement before any tissues are transferred.
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View all literature mentionsThis polyclonal targets MBD2ab (RA-18) antibody produced in rabbit
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