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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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Submitted November 4, 2008
Accepted February 27, 2009

Exclusive expression of proteasome subunit {beta}5t in the human thymic cortex

Utano Tomaru*, Akihiro Ishizu, Shigeo Murata, Yukiko Miyatake, Sayuri Suzuki, Satomi Takahashi, Taku Kazamaki, Jiro Ohara, Tomohisa Baba, Sari Iwasaki, Kazunori Fugo, Noriyuki Otsuka, Keiji Tanaka, and Masanori Kasahara

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

* Corresponding author; email: tomaruu{at}med.hokudai.ac.jp.

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 {beta} subunits, {beta}1, {beta}2, and {beta}5, of the 20S proteasome. Recently, a novel {beta} subunit expressed exclusively in cortical thymic epithelial cells was discovered in mice. This subunit, designated {beta}5t, 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 {beta}5t is expressed exclusively in the thymic cortex. Human {beta}5t was expressed in approximately 80% of cortical thymic epithelial cells and some cortical dendritic cells. Human {beta}5t was incorporated into proteasomes with two other catalytically active {beta} subunits {beta}1i and {beta}2i, 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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