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Recruitment of SMURF1 (Ebisawa et al. 2001), SMURF2 (Kavsak et al. 2000) or NEDD4L (Kuratomi et al. 2005) to the activated TGF-beta receptor complex by SMAD7 and subsequent ubiquitination of SMAD7 and/or TGFBR1 triggers degradation of SMAD7 and TGFBR1 through proteasome and lysosome-dependent routes, resulting in downregulation of signaling by TGF-beta receptors.