Screen for multi-SUMO-binding proteins reveals a multi-SIM-binding mechanism for recruitment of the transcriptional regulator ZMYM2 to chromatin.
Protein SUMOylation has emerged as an important regulatory event, particularly in nuclear processes such as transcriptional control and DNA repair. In this context, small ubiquitin-like modifier (SUMO) often provides a binding platform for the recruitment of proteins via their SUMO-interacting motifs (SIMs). Recent discoveries point to an important role for multivalent SUMO binding through multiple SIMs in the binding partner as exemplified by poly-SUMOylation acting as a binding platform for ubiquitin E3 ligases such as ring finger protein 4. Here, we have investigated whether other types of protein are recruited through multivalent SUMO interactions. We have identified dozens of proteins that bind to multi-SUMO platforms, thereby uncovering a complex potential regulatory network. Multi-SUMO binding is mediated through multi-SIM modules, and the functional importance of these interactions is demonstrated for the transcriptional corepressor ZMYM2/ZNF198 where its multi-SUMO-binding activity is required for its recruitment to chromatin.
Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom;
Elisa
E
Aguilar-Martinez
Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom;
Xi
X
Chen
Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom;
Aaron
A
Webber
Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom;
A Paul
AP
Mould
Centre for Gene Regulation and Expression, University of Dundee, Dundee DD1 5EH, United Kingdom.
Anne
A
Seifert
Centre for Gene Regulation and Expression, University of Dundee, Dundee DD1 5EH, United Kingdom.
Ronald T
RT
Hay
Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom; a.d.sharrocks@manchester.ac.uk.
Andrew D
AD
Sharrocks
D002843:Chromatin / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D011485:Protein Binding; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
D002843:Chromatin; D004268:DNA-Binding Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D014157:Transcription Factors; C111777:ZMYM2 protein, human
SIM; SUMO; ZMYM2; ZNF198; chromatin