Figure 3.

Structure of SH3 domain-binding protein 2 (SH3BP2) and increased SH3BP2 accumulation in SH3BP2 cherubism mutant cells. (a) Structure of SH3BP2. SH3BP2 protein consists of three modular domains, namely, pleckstrin homology (PH), SH3-binding, and SH2 domains. Cherubism mutations are located within the RSPPDG sequence. (b) Tankyrase recognizes wild-type SH3BP2 protein through the RSPPDG sequence and then induces PARsylation and subsequent degradation of SH3BP2 protein. (c) The mutated SH3BP2 sequence disrupts the recognition of tankyrase. The mutant protein escapes from the degradation process, resulting in aberrant accumulation in the cytoplasm.