Siergiejuk, E., Scott, D. C., Schulman, B. A., Hofmann, K., Kurz, T. and Peter, M. (2009) Cullin neddylation and substrate-adaptors counteract SCF inhibition by the CAND1-like protein Lag2 in Saccharomyces cerevisiae. EMBO Journal, 28(24), pp. 3845-3856. (doi: 10.1038/emboj.2009.354) (PMID:19942853) (PMCID:PMC2797064)
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Abstract
Cullin‐based E3 ubiquitin ligases are activated through covalent modification of the cullin subunit by the ubiquitin‐like protein Nedd8. Cullin neddylation dissociates the ligase assembly inhibitor Cand1, and promotes E2 recruitment and ubiquitin transfer by inducing a conformational change. Here, we have identified and characterized Lag2 as a likely Saccharomyces cerevisiae orthologue of mammalian Cand1. Similar to Cand1, Lag2 directly interacts with non‐neddylated yeast cullin Cdc53 and prevents its neddylation in vivo and in vitro. Binding occurs through a conserved C‐terminal β‐hairpin structure that inserts into the Skp1‐binding pocket on the cullin, and an N‐terminal motif that covers the neddylation lysine. Interestingly, Lag2 is itself neddylated in vivo on a lysine adjacent to this N‐terminal‐binding site. Overexpression of Lag2 inhibits Cdc53 activity in strains defective for Skp1 or neddylation functions, implying that these activities are important to counteract Lag2 in vivo. Our results favour a model in which binding of substrate‐specific adaptors triggers release of Cand1/Lag2, whereas subsequent neddylation of the cullin facilitates the removal and prevents re‐association of Lag2/Cand1.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Kurz, Dr Thimo |
| Authors: | Siergiejuk, E., Scott, D. C., Schulman, B. A., Hofmann, K., Kurz, T., and Peter, M. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Molecular Biosciences |
| Journal Name: | EMBO Journal |
| Publisher: | EMBO Press |
| ISSN: | 0261-4189 |
| ISSN (Online): | 1460-2075 |
| Published Online: | 26 November 2009 |
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