Forced interaction of cell surface proteins with Derlin-1 in the endoplasmic reticulum is sufficient to induce their dislocation into the cytosol for degradation

► A MHC-I hybrid containing the US11 TMD is degraded via ERAD without US11. ► A viral protein containing the US11 TMD is also degraded via Derlin-1-dependent ERAD. ► Derlin-1 may interact with ERAD substrates throughout the dislocation process.