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Covalent modification of all members of human cullin family proteins by NEDD8

Oncogene volume 18, pages 6829–6834 (1999)Cite this article

Abstract

Recently we found that NEDD8, a ubiquitin-like protein, was linked covalently to human cullin-4A (abbreviated Cul-4A) by a new ubiquitin-related pathway that is analogous to but distinct from the ligating system for SUMO1, another ubiquitin-like protein. However, it remained unknown whether the other five members of the family of human cullin/Cdc53 proteins are modified by NEDD8. Here we report that all Hs-Cul family proteins, such as Cul-1, Cul-2, Cul-3, Cul-4B, and Cul-5, in addition to Cul-4A, were modified by covalent attachment of NEDD8 in rabbit reticulocyte lysates. Moreover, by comprehensive Northern-blot analyses, we examined multiple tissue distributions of the messages for all Cul-family proteins, NEDD8, and the NEDD8-ligating system consisting of APP-BP1/hUba3, and hUbc12, which function as E1- and E2-like enzymes, respectively. The expressions of Cul-1, Cul-2, and Cul-3 resembled each other and were apparently correlated to those of NEDD8 and the NEDD8-ligating system in various human cells and tissues. However, the mRNA levels of Cul-4A, Cul-4B, and Cul-5 differed considerably from each other as well as from other Cul-family proteins. The enhanced expression of all Cul-family proteins except Cul-5 was observed in a variety of tumor cell lines.

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Acknowledgements

This work was supported in part by grants from the program Grants-in-aid for Scientific Research on Priority Areas (Intracellular Proteolysis) from the Ministry of Education, Science, Sports, and Culture of Japan, and the Human Frontier Science Promotion Organization (K Tanaka).

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Authors and Affiliations

  1. The Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-0021, Japan

    Tomoko Hori, Tomoki Chiba & Keiji Tanaka

  2. Hoffmann-La Roche Inc., 340 Kingsland Street, Nutley, 07110-1199, New Jersey, NJ, USA

    Chikara Miyamoto

  3. Kato Cytoprotein Network Project, ERATO, Japan Science and Technology Corporation (JST), c/o Sagami Chemical Research Center, Nishi-ohnuma 4-4-1, Sagamihara, 229-0012, Kanagawa, Japan

    Fumio Osaka & Seishi Kato

  4. Biomedical R&D Department, Sumitomo Electric Industries, 1, Taya-cho, Sakae-ku, 244-8588, Yokohama, Japan

    Ken Okabayashi & Naoki Shimbara

  5. Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation (JST), Japan

    Tomoko Hori, Tomoki Chiba, Ken Okabayashi, Naoki Shimbara & Keiji Tanaka

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  1. Tomoko Hori
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Hori, T., Osaka, F., Chiba, T. et al. Covalent modification of all members of human cullin family proteins by NEDD8. Oncogene 18, 6829–6834 (1999). https://doi.org/10.1038/sj.onc.1203093

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