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  • The EMBO Journal (2006) 25, 4524 - 4536
  • doi:10.1038/sj.emboj.7601338

Published online: 21 September 2006

A novel proteasome interacting protein recruits the deubiquitinating enzyme UCH37 to 26S proteasomes

Jun Hamazaki1,2, Shun-ichiro Iemura3, Tohru Natsume3, Hideki Yashiroda1, Keiji Tanaka1 and Shigeo Murata1,4

  1. Laboratory of Frontier Science, Core Technology and Research Center, Tokyo Metropolitan Institute of Medical Science, Bunkyko-ku, Tokyo, Japan
  2. Department of Biological Sciences, Graduate School of Science, Tokyo Metropolitan University, Hachiohji, Tokyo, Japan
  3. National Institutes of Advanced Industrial Science and Technology, Biological Information Research Center, Kohtoh-ku, Tokyo, Japan
  4. PRESTO, Japan Science and Technology Agency, Kawaguchi, Saitama, Japan

Correspondence to:

Shigeo Murata, Laboratory of Frontier Science, Core Technology and Research Center, Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyko-ku, Tokyo 113-9613, Japan. Tel./Fax: +81 3 3823 2237; E-mail: smurata@rinshoken.or.jp

Received 21 February 2006; Accepted 15 August 2006

The 26S proteasome is a multisubunit protease responsible for regulated proteolysis in eukaryotic cells. It is composed of one catalytic 20S proteasome and two 19S regulatory particles attached on both ends of 20S proteasomes. Here, we describe the identification of Adrm1 as a novel proteasome interacting protein in mammalian cells. Although the overall sequence of Adrm1 has weak homology with the yeast Rpn13, the amino- and carboxyl-terminal regions exhibit significant homology. Therefore, we designated it as hRpn13. hRpn13 interacts with a base subunit Rpn2 via its amino-terminus. The majority of 26S proteasomes contain hRpn13, but a portion of them does not, indicating that hRpn13 is not an integral subunit. Intriguingly, we found that hRpn13 recruits UCH37, a deubiquitinating enzyme known to associate with 26 proteasomes. The carboxyl-terminal regions containing KEKE motifs of both hRpn13 and UCH37 are involved in their physical interaction. Knockdown of hRpn13 caused no obvious proteolytic defect but loss of UCH37 proteins and decrease in deubiquitinating activity of 26S proteasomes. Our results indicate that hRpn13 is essential for the activity of UCH37.

  • Keywords:

    • deubiquitinating enzyme,
    • proteasome,
    • Rpn13,
    • ubiquitin,
    • UCH37