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Covalent modifier NEDD8 is essential for SCF ubiquitin‐ligase in fission yeast

Fumio Osaka, Mihoro Saeki, Satoshi Katayama, Noriko Aida, Akio Toh‐e, Kin‐ichiro Kominami, Takashi Toda, Toshiaki Suzuki, Tomoki Chiba, Keiji Tanaka, Seishi Kato

Author Affiliations

  1. Fumio Osaka1,
  2. Mihoro Saeki1,
  3. Satoshi Katayama2,
  4. Noriko Aida1,
  5. Akio Toh‐e3,
  6. Kin‐ichiro Kominami2,4,
  7. Takashi Toda2,
  8. Toshiaki Suzuki5,
  9. Tomoki Chiba5,
  10. Keiji Tanaka5 and
  11. Seishi Kato*,1
  1. 1 Kato 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
  2. 2 Laboratory of Cell Regulation, Imperial Cancer Research Fund (ICRF), London, WC2A 3PX, UK
  3. 3 Department of Biological Sciences, Graduate School of Science, University of Tokyo, 7‐3‐1 Hongo, Tokyo, 113‐0033
  4. 4 Present address: Medical Institute of Bioregulation, Kyushu University, 3‐1‐1 Maidashi, Higashi‐ku, Fukuoka, 812‐8582, Japan
  5. 5 The Tokyo Metropolitan Institute of Medical Science, and CREST, Japan Science and Technology Corporation (JST), 3‐18‐22 Honkomagome, Bunkyo‐ku, Tokyo, 113‐8613, Japan
  1. *Corresponding author. E-mail: seishi{at}sagami.ne.jp
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Abstract

A ubiquitin‐like modifier, NEDD8, is covalently attached to cullin‐family proteins, but its physiological role is poorly understood. Here we report that the NEDD8‐modifying pathway is essential for cell viability and function of Pcu1 (cullin‐1 orthologue) in fission yeast. Pcu1 assembled on SCF ubiquitin‐ligase was completely modified by NEDD8. Pcu1K713R defective for NEDD8 conjugation lost the ability to complement lethality due to pcu1 deletion. Forced expression of Pcu1K713R or depletion of NEDD8 in cells resulted in impaired cell proliferation and marked stabilization of the cyclin‐dependent kinase inhibitor Rum1, which is a substrate of the SCF complex. Based on these findings, we propose that covalent modification of cullin‐1 by the NEDD8 system plays an essential role in the function of SCF in fission yeast.

  • Received January 11, 2000.
  • Revision received May 4, 2000.
  • Accepted May 9, 2000.
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