A heterodimeric complex that promotes the assembly of mammalian 20S proteasomes (original) (raw)

Nature volume 437, pages 1381–1385 (2005)Cite this article

Abstract

The 26S proteasome is a multisubunit protease responsible for regulated proteolysis in eukaryotic cells1,2. It comprises one catalytic 20S proteasome and two axially positioned 19S regulatory complexes3. The 20S proteasome is composed of 28 subunits arranged in a cylindrical particle as four heteroheptameric rings, α1–7β1–7β1–7α1–7 (refs 4, 5), but the mechanism responsible for the assembly of such a complex structure remains elusive. Here we report two chaperones, designated proteasome assembling chaperone-1 (PAC1) and PAC2, that are involved in the maturation of mammalian 20S proteasomes. PAC1 and PAC2 associate as heterodimers with proteasome precursors and are degraded after formation of the 20S proteasome is completed. Overexpression of PAC1 or PAC2 accelerates the formation of precursor proteasomes, whereas knockdown by short interfering RNA impairs it, resulting in poor maturation of 20S proteasomes. Furthermore, the PAC complex provides a scaffold for α-ring formation and keeps the α-rings competent for the subsequent formation of half-proteasomes. Thus, our results identify a mechanism for the correct assembly of 20S proteasomes.

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Acknowledgements

We thank Y. Murakami for the ornithine decarboxylase degradation assay system, K. Furuyama for technical support, and D. Finley for comments on the manuscript. This work was supported by grants from the Japanese Science and Technology Agency (to S.M.), the Ministry of Education, Science and Culture of Japan (to S.M. and K.T.) and the New Energy and Industrial Technology Development Organization (to T.N.). Y.H. was supported by the Japanese Society for the Promotion of Science.

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Authors and Affiliations

  1. Laboratory of Frontier Science, Core Technology and Research Center, Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo, 113-8613, Japan
    Yuko Hirano, Hideki Yashiroda, Keiji Tanaka & Shigeo Murata
  2. Institute of Molecular Biology and Physiology, University of Copenhagen, 13 Universitetsparken, DK 2100, Copenhagen, Denmark
    Klavs B. Hendil
  3. National Institute of Advanced Industrial Science and Technology, Biological Information Research Center, Kohtoh-ku, Tokyo, 135-0064, Japan
    Shun-ichiro Iemura, Ryoichi Nagane, Yusaku Hioki & Tohru Natsume
  4. PRESTO, Japan Science and Technology Agency, Kawaguchi, Saitama, 332-0012, Japan
    Shigeo Murata

Authors

  1. Yuko Hirano
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  2. Klavs B. Hendil
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  3. Hideki Yashiroda
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  4. Shun-ichiro Iemura
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  5. Ryoichi Nagane
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  6. Yusaku Hioki
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  7. Tohru Natsume
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  8. Keiji Tanaka
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  9. Shigeo Murata
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Corresponding authors

Correspondence toKeiji Tanaka or Shigeo Murata.

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Competing interests

The sequences for human PAC1 and PAC2 have been deposited in GenBank under accession numbers BR000236 and BR000237, respectively. Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.

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Hirano, Y., Hendil, K., Yashiroda, H. et al. A heterodimeric complex that promotes the assembly of mammalian 20S proteasomes.Nature 437, 1381–1385 (2005). https://doi.org/10.1038/nature04106

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