J. Exp. Med., Volume 187, Number 1, January 5, 1998 97-104

Immunoproteasome Assembly: Cooperative Incorporation of Interferon  (IFN-)-inducible Subunits

By Thomas A. Griffin,^* Dipankar Nandi, Miguel Cruz, Hans Jörg Fehling, Luc Van Kaer,^¶ John J. Monaco,^§ and Robert A. Colbert^*

From the ^* William S. Rowe Division of Rheumatology, Children's Hospital Medical Center, Cincinnati, Ohio 45229;  Department of Molecular Genetics and the ^§ Howard Hughes Medical Institute, University of Cincinnati School of Medicine, Cincinnati, Ohio 45267;  Basel Institute for Immunology, CH-4005 Basel, Switzerland; and the ^¶ Howard Hughes Medical Institute and Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232

LMP2, LMP7, and MECL are interferon -inducible catalytic subunits of vertebrate 20S proteasomes, which can replace constitutive catalytic subunits (delta, X, and Z, respectively) during proteasome biogenesis. We demonstrate that MECL requires LMP2 for efficient incorporation into preproteasomes, and preproteasomes containing LMP2 and MECL require LMP7 for efficient maturation. The latter effect depends on the presequence of LMP7, but not on LMP7 catalytic activity. This cooperative mechanism favors the assembly of homogeneous "immunoproteasomes" containing all three inducible subunits, suggesting that these subunits act in concert to enhance proteasomal generation of major histocompatibility complex class I-binding peptides.

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