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Blood, 21 May 2009, Vol. 113, No. 21, pp. 5186-5191.
Prepublished online as a Blood First Edition Paper on March 16, 2009; DOI 10.1182/blood-2008-11-187633.


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IMMUNOBIOLOGY

Exclusive expression of proteasome subunit β5t in the human thymic cortex

Utano Tomaru1, Akihiro Ishizu2, Shigeo Murata3, Yukiko Miyatake1, Sayuri Suzuki1, Satomi Takahashi1, Taku Kazamaki1, Jiro Ohara1, Tomohisa Baba4, Sari Iwasaki1, Kazunori Fugo1, Noriyuki Otsuka1, Keiji Tanaka5, and Masanori Kasahara1

1 Department of Pathology, Hokkaido University Graduate School of Medicine, Sapporo; 2 Faculty of Health Sciences, Hokkaido University, Sapporo; 3 Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Science, The University of Tokyo, Tokyo; 4 Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa; and 5 Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan

The ubiquitin-proteasome pathway, which degrades intracellular proteins, is involved in numerous cellular processes, including the supply of immunocompetent peptides to the antigen presenting machinery. Proteolysis by proteasomes is conducted by three β subunits, β1, β2, and β5, of the 20S proteasome. Recently, a novel β subunit expressed exclusively in cortical thymic epithelial cells was discovered in mice. This subunit, designated β5t, is a component of the thymoproteasome, a specialized type of proteasomes implicated in thymic positive selection. In this study, we show that, like its mouse counterpart, human β5t is expressed exclusively in the thymic cortex. Human β5t was expressed in approximately 80% of cortical thymic epithelial cells and some cortical dendritic cells. Human β5t was incorporated into proteasomes with two other catalytically active β subunits β1i and β2i, forming 20S proteasomes with subunit compositions characteristic of thymoproteasomes. The present study demonstrates, for the first time, the existence of thymoproteasomes in the human thymic cortex, indicating that thymoproteasome function is likely conserved between humans and mice.


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