The ubiquitin E3 ligase RNF181 transfers ubiquitin from the E2-ubiquitin conjugate (UBE2D1, UBE2D2, UBE2D3, UBE2E1, UBE2B, or UBE2N) to BCL10 (Pedersen et al. 2015). RNF181, which can interact with CARD11, appears to act on BCL10 before BCL10 is recruited to activated (phosphorylated) CARD11. The resulting lysine-48 polyubiquitinated BCL10 is degraded by the proteasome, resulting in attenuation of T cell receptor signaling downstream of CARD11 (Pedersen et al. 2015).