Cherubism, autosomal-dominant syndrome, is caused by mutations in Sh3bp2, the gene that encodes the adaptor protein 3BP2. In this manuscript the authors show that Tankyrase, a member of the poly(ADP-ribose)polymerase (PARP) family, regulates 3BP2 stability through ADP-ribosylation and subsequent ubiquitylation by the E3-ubiquitin ligase RNF146 in osteoclasts. Cherubism mutations uncouple 3BP2 from Tankyrase-mediated protein destruction, which results in its stabilization and subsequent hyperactivation of the SRC, SYK, and VAV signaling pathways.
http://www.cell.com/retrieve/pii/S0092867411013493