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