Fig. 6: Model for TPSN regulation by the RNF185/MBRL ERAD complex.

The RNF185/MBRL complex degrades a pool of unassembled TPSN, thereby limiting the amount available for assembly onto the PLC. RNF185/MBRL-dependent degradation involves the recognition of evolutionary conserved lysine residue in the TPSN transmembrane segment that is also essential for its assembly with TAP1 and TAP2. The absence of RNF185/MBRL results in elevated TPSN levels. These stabilize its partners TAP1 and TAP and ultimately result in increased levels of MHC-I. See text for details.