Abstract
Protein SUMOylation represents an important regulatory event that changes the activities of numerous proteins. Recent evidence demonstrates that polySUMO chains can act as a trigger to direct the ubiquitin ligase RNF4 to substrates to cause their turnover through the ubiquitin pathway. RNF4 uses multiple SUMO interaction motifs (SIMs) to bind to these chains. However, in addition to polySUMO chains, a multimeric binding surface created by the simultaneous SUMOylation of multiple residues on a protein or complex could also provide a platform for the recruitment of multi-SIM proteins like RNF4. Here we demonstrate that multiSUMOylated ETV4 can bind to RNF4 and that a unique combination of SIMs is required for RNF4 to interact with this multiSUMOylated platform. Thus RNF4 can bind to proteins that are either polySUMOylated through a single site or multiSUMOylated on several sites and raises the possibility that such multiSIM-multiSUMO interactions might be more widespread.
Highlights
SUMOylation is a process whereby proteins are modified by SUMO through conjugation to specific lysine residues
Multiple high molecular weight SUMO conjugates were observed in the presence of wild-type SUMO3 (Figure 1B, lanes 3 and 4) and an identical pattern of conjugation was observed in the presence of SUMO3(K11R) (Figure 1B, lanes 5 and 6)
One of the major mechanisms through which SUMOylation affects target protein activity is through providing a binding platform for other proteins. This can be elicited through the conjugation of single SUMO moieties, or through the subsequent formation of polySUMO chains on top of these initial conjugation events. These polySUMO chains act as a binding platform for SUMO targeted ubiquitin ligase (STUbL) such as RNF4, which subsequently target the SUMOylated protein for ubiquitination and degradation (Boutell et al, 2011; Lescasse et al, 2013; Sun & Hunter, 2012; Tatham et al, 2008)
Summary
SUMOylation is a process whereby proteins are modified by SUMO (small ubiquitin-like modifier) through conjugation to specific lysine residues. Proteins are typically modified by a single SUMO molecule by conjugation to specific lysine residues While this is the case for SUMO1, both SUMO2 and SUMO3 can develop SUMO chains through conjugation of additional SUMO moieties through a lysine residue located within the N-terminal region of these proteins (reviewed in Ulrich, 2008). This leads to the deposition of SUMO chains on substrates which provide a polymeric binding surface for targeting new protein-protein interactions. This type of interaction has been exploited by proteins like RNF4 which has multiple SIMs which can simultaneously interact with several SUMO moieties in polymeric SUMO chains (Keusekotten et al, 2014; Kung et al, 2014; Tatham et al, 2008; Xu et al, 2014)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
