Cop9/signalosome subunits and Pcu4 regulate ribonucleotide reductase by both checkpoint-dependent and -independent mechanisms
Abstract
The signalosome is implicated in regulating cullin-dependent ubiquitin ligases. We find that two signalosome subunits, Csn1 and Csn2, are required to regulate ribonucleotide reductase (RNR) through the degradation of a small protein, Spd1, that acts to anchor the small RNR subunit in the nucleus. Spd1 destruction correlates with the nuclear export of the small RNR subunit, which, in turn, correlates with a requirement for RNR in replication and repair. Spd1 degradation is promoted by two separate CSN-dependent mechanisms. During unperturbed S phase, Spd1 degradation is independent of checkpoint proteins. In irradiated G2 cells, Spd1 degradation requires the DNA damage checkpoint. The signalosome copurifies with Pcu4 (cullin 4). Pcu4, Csn1, and Csn2 promote the degradation of Spd1, identifying a new function for the signalosome as a regulator of Pcu4-containing E3 ubiquitin ligase.
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Footnotes
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↵4 These authors contributed equally to this work.
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Present addresses: 5ESBA Tech AG, Wagistrasse 21, CH-8952 Zurich Schlieren, Switzerland. 6Pieris Proteolab AG, Lise-Meitner-Strasse 30, D-85354 Freising, Germany.
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↵7 Corresponding author.
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E-MAIL a.m.carr{at}sussex.ac.uk; FAX 44-1273-678121.
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Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.1090803.
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- Received February 28, 2003.
- Accepted March 7, 2003.
- Cold Spring Harbor Laboratory Press
