The subunits MECL-1 and LMP2 are mutually required for incorporation into the 20S proteasome

Processing of antigens for presentation by major histocompatibility complex (MHC) class I molecules requires the activity of the proteasome, The 20S proteasome complex is composed of 14 different subunits, 2 of which can be substituted by the interferon gamma (IFN-gamma)-inducible and MHC-encoded subunits LMP2 and LMP7 (low molecular mass polypeptides 2 and 7), A third subunit, MECL-1, is inducible by IFN-gamma but is encoded outside the MHC. Here we show-by cotransfection experiments that the incorporation of MECL-1 into the 20S proteasome is directly dependent on the expression of LMP2 but independent of LMP7. Conversely, the uptake of LMP2 is strongly enhanced by MECL-1 expression, The expression of MECL-1 caused a replacement of the homologous subunit Z in the 20S proteasome complex, LMP2 is required for MECL-1 incorporation at the level of proteasome precursor formation that guarantees the concerted incorporation of two IFN-gamma-inducible proteasome subunits encoded inside and outside the MHC, The obligatory coin-corporation of MECL-1 and LMP2 is an important parameter for the interpretation of results obtained with LMP2-deficient cell lines and mice as well as for the design of experiments addressing the function of MECL-1 in antigen presentation.