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| Subject Categories: Signal Transduction | Genome Stability & Dynamics |
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| The EMBO Journal
(2007) 26, 4102–4112, doi:10.1038/sj.emboj.7601839 Published online 30 August 2007 |
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| Conserved function of RNF4 family proteins in eukaryotes: targeting a ubiquitin ligase to SUMOylated proteins |
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| Huaiyu Sun, Joel D Leverson1 and Tony Hunter |
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Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA To whom correspondence should be addressed Tony Hunter, Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. Tel.: +1 858 453 4100 ext 1385; Fax: +1 858 457 4765; E-mail: hunter@salk.edu 1 Present address: Abbott Laboratories, Global Pharmaceutical Research Division, Cancer Division, 100 Abbott Park Road, Abbott Park, IL 60064, USA Received 11 May 2007; Accepted 2 August 2007; Published online 30 August 2007. |
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| Abstract |
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| The function of small ubiquitin-like modifier (SUMO)-binding proteins is key to understanding how SUMOylation regulates cellular processes. We identified two related Schizosaccharomyces pombe proteins, Rfp1 and Rfp2, each having an N-terminal SUMO-interacting motif (SIM) and a C-terminal RING-finger domain. Genetic analysis shows that Rfp1 and Rfp2 have redundant functions; together, they are essential for cell growth and genome stability. Mammalian RNF4, an active ubiquitin E3 ligase, is an orthologue of Rfp1/Rfp2. Rfp1 and Rfp2 lack E3 activity but recruit Slx8, an active RING-finger ubiquitin ligase, through a RING–RING interaction, to form a functional E3. RNF4 complements the growth and genomic stability defects of rfp1rfp2, slx8, and rfp1rfp2slx8 mutant cells. Both the Rfp-Slx8 complex and RNF4 specifically ubiquitylate artificial SUMO-containing substrates in vitro in a SUMO binding-dependent manner. SUMOylated proteins accumulate in rfp1rfp2 double-null cells, suggesting that Rfp/Slx8 proteins may promote ubiquitin-dependent degradation of SUMOylated targets. Hence, we describe a family of SIM-containing RING-finger proteins that potentially regulates eukaryotic genome stability through linking SUMO-interaction with ubiquitin conjugation. |
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| Keywords: SUMO, SUMO-interacting motif, ubiquitin, RING, E3 ligase |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSNature Cell Biology News and Views (01 Sep 2000) Nature Cell Biology News and Views (01 May 2008) RESEARCHX-ray structure of 5-aminolaevulinate dehydratase, a hybrid aldolase Nature Structural Biology Article (01 Dec 1997) SUMO-targeted ubiquitin ligases in genome stability The EMBO Journal Article (19 Sep 2007) |
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