Fig. 2.

Functions, mechanisms, and regulation of HECTD3. HECTD3 targets several apoptosis-related proteins (MALT1, caspase-8, and caspase-9) for nondegradative polyubiquitination and confers drug resistance to cancer cell. It also regulates the immune response through nondegradative polyubiquitination of STAT3, MALT1, and TRAF3. In addition to the nondegradative pathway, HECTD3 mediates ubiquitin–proteasome degradation of Tara and CRAF. HER2/ERK and miR-153 regulate the HECTD3 activity and expression. The linkage types of polyubiquitin chain and the modification sites in the substrate proteins are indicated