Smad Specific E3 Ubiquitin Protein Ligase 2 (SMURF2)

SMURF2, a 748-amino acid ubiquitin E3 ligase that is 83% identical to SMURF1.SMURF2 was nuclear, but binding to SMAD7 induced export and recruitment to the activated transforming growth factor-beta receptor (TGFBR), where it caused degradation of receptors and of SMAD7 via proteasomal and lysosomal pathways. Gamma-interferon (IFNG), which stimulates expression of SMAD7, induced SMAD7-SMURF2 complex formation and increased TGFBR turnover, which was stabilized by blocking SMAD7 or SMURF2 expression. Furthermore, SMAD7 mutants that interfered with recruitment of SMURF2 to the receptors were compromised in their inhibitory activity. These studies defined SMAD7 as an adaptor in an E3 ubiquitin ligase complex that targets TGFBR for degradation.