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Transactivation of Schizosaccharomyces pombe cdt2 + stimulates a Pcu4–Ddb1–CSN ubiquitin ligase
Author(s) -
Liu Cong,
Poitelea Marius,
Watson Adam,
Yoshida Shuhei,
Shimoda Chikashi,
Holmberg Christian,
Nielsen Olaf,
Carr Antony M
Publication year - 2005
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600854
Subject(s) - biology , cullin , cop9 signalosome , ubiquitin ligase , ddb1 , ubiquitin , schizosaccharomyces , schizosaccharomyces pombe , protein subunit , microbiology and biotechnology , dna repair , genetics , protein degradation , neddylation , dna , gene , biochemistry , saccharomyces cerevisiae , protease , peptide hydrolases , enzyme
Cullin‐4 forms a scaffold for multiple ubiquitin ligases. In Schizosaccharomyces pombe , the Cullin‐4 homologue (Pcu4) physically associates with Ddb1 and the COP9 signalosome (CSN). One target of this complex is Spd1. Spd1 regulates ribonucleotide reductase (RNR) activity. Spd1 degradation during S phase, or following DNA damage of G2 cells, results in the nuclear export of the small RNR subunit. We demonstrate that Cdt2, an unstable WD40 protein, is a regulatory subunit of Pcu4–Ddb1–CSN ubiquitin ligase. cdt2 deletion stabilises Spd1 and prevents relocalisation of the small RNR subunit from the nucleus to the cytoplasm. cdt2 + is periodically transcribed by the Cdc10/DSC1 transcription factor during S phase and transiently transcribed following DNA damage of G2 cells, corresponding to Spd1 degradation profiles. Cdt2 co‐precipitates with Spd1, and Cdt2 overexpression results in constitutive Spd1 degradation. We propose that Cdt2 incorporation into the Pcu4–Ddb1–CSN complex prompts Spd1 targeting and subsequent degradation and that Cdt2 is a WD40 repeat adaptor protein for Cullin‐4‐based ubiquitin ligase.