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| Short report |
| Covalent modification of all members of human cullin family proteins by NEDD8 |
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| Tomoko Hori1,5, Fumio Osaka3, Tomoki Chiba1,5, Chikara Miyamoto2, Ken Okabayashi4,5, Naoki Shimbara4,5, Seishi Kato3 and Keiji Tanaka1,5 |
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1The Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-0021, Japan
2Hoffmann-La Roche Inc., 340 Kingsland Street, Nutley, New Jersey, NJ 07110-1199, USA
3Kato Cytoprotein Network Project, ERATO, Japan Science and Technology Corporation (JST), c/o Sagami Chemical Research Center, Nishi-ohnuma 4-4-1, Sagamihara, Kanagawa 229-0012, Japan
4Biomedical R&D Department, Sumitomo Electric Industries, 1, Taya-cho, Sakae-ku, Yokohama 244-8588, Japan
5Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation (JST), Japan
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Correspondence to: Keiji Tanaka, The Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-0021, Japan
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| 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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| Keywords |
| cullin; NEDD8; SCF; ubiquitin; ubiquitin-like protein |
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| Received 29 March 1999; revised 12 July 1999; accepted 14 July 1999 |
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| 18 November 1999, Volume 18, Number 48, Pages 6829-6834 |
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