Article
- The EMBO Journal (2007) 26, 4102 - 4112
- doi:10.1038/sj.emboj.7601839
Published online: 30 August 2007
Subject Categories:
Conserved function of RNF4 family proteins in eukaryotes: targeting a ubiquitin ligase to SUMOylated proteins
Huaiyu Sun1, Joel D Leverson1,a and Tony Hunter1
- Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA
Correspondence to:
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
aPresent 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
Abstract
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.
Keywords:
- SUMO,
- SUMO-interacting motif,
- ubiquitin,
- RING,
- E3 ligase
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